SWI/SNF Inactivation in Disease: Comparison
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Please note this is a comparison between Version 1 by Álvaro Andrades and Version 3 by Dean Liu.

Mammalian SWI/SNF (SWitch/Sucrose Non-Fermentable) complexes are ATP-dependent chromatin remodelers. Many SWI/SNF members, such as ARID1A and SMARCA4, have emerged among the most frequently mutated genes in certain diseases, especially cancer. Overall, the SWI/SNF complex is the most mutated chromatin remodeling complex across multiple cancers, highlighting its central role in tumorigenesis.

  • SWI/SNF complex
  • lung cancer
  • lung adenocarcinoma

1. Introduction

SWI/SNF (SWitch/Sucrose Non-Fermentable) complexes are ATP-dependent chromatin remodeling complexes that control gene expression by altering the positioning of nucleosomes and recruiting other chromatin binding factors[1][2]. SWI/SNF complexes were discovered in yeast as modulators of mating-type switching (“SWI”) and of growth on sucrose media (“SNF”)[3][4]. Today, advances in proteomics, biochemistry, molecular biology, and structural biology have substantially improved the knowledge of SWI/SNF composition, assembly, and function in mammals, including humans. In the latter, SWI/SNF complexes can be constituted by different combinations of 10-15 subunits out of 29 possible subunits[5]. The specific combinations of subunits that form SWI/SNF complexes in a cell at a given time point depend on the cell type and on the context[6]. Overall, three major SWI/SNF complexes have been identified in mammals: canonical BAF (cBAF), polybromo-associated BAF (PBAF), and noncanonical BAF (ncBAF), each of which is constituted by a combination of common and complex-specific subunits. In all cases, complexes contain one catalytic ATPase subunit, which can be either SMARCA4 (previously known as BRG1) or SMARCA2 (previously known as BRM). In addition, certain groups of SWI/SNF subunits are paralogs that have similar functions so that, when one subunit is missing, a paralog subunit can take its place. However, these changes may alter some of the functions of the complexes[7].

SWI/SNF complexes can exert their functions through various mechanisms. The main mechanism is using the energy from the hydrolysis of ATP to eject nucleosomes and, thus, to reorganize chromatin[8]. However, other mechanisms have been suggested for certain SWI/SNF functions. For example, certain SWI/SNF subunits may interact with other chromatin-modifying enzymes to activate promoters or enhancers[9]. Moreover, SWI/SNF complexes are recruited to DNA damage sites, where they participate in DNA damage response pathways[10][11][12]. Finally, SWI/SNF complexes participate in the 3D organization of chromosomes by interacting with CTCF binding sites, cohesins, lamin, and replication origins[13].

As a consequence of the diversity of SWI/SNF complexes and their genome-wide mechanisms of action, their biological functions are highly heterogeneous, dynamic, and context-dependent. During development, certain SWI/SNF subunits have been associated with embryogenesis and with differentiation into various cell types (reviewed in [14]). In differentiated cells, SWI/SNF complexes keep playing an essential role in the dynamic regulation of gene expression, genome organization, and DNA repair. Accordingly, deficiencies or alterations in SWI/SNF subunits are associated with disease, especially developmental disorders and cancer.

 

2. Alterations of SWI/SNF complexes in disease

2.1. Neurodevelopmental disorders

SWI/SNF complexes are essential for development, and specific SWI/SNF complexes guide the differentiation of embryonic stem cells into neurons[15]. Alterations in SWI/SNF subunits can lead to neurodevelopmental disorders (NDDs), which manifest as intellectual disabilities that may or may not be accompanied by other symptoms. For example, heterozygous germline mutations in various SWI/SNF subunits can lead to a rare NDD called Coffin-Siris syndrome (CSS; OMIM #135900). The most commonly mutated subunit in CSS patients is ARID1B, followed by ARID1A, SMARCB1, SMARCA4, SMARCA2, and SMARCE1[16]. Another example is the Nicolaides-Baraitser syndrome (OMIM #601358), which is caused by missense mutations in SMARCA2[17].

 

2.2. Cancer

2.2.1. Mutations

During tumor development, cancer cells accumulate somatic mutations in a wide variety of genes. The mutations that contribute to the tumor phenotype are named ‘driver mutations’. While different cancer types tend to accumulate mutations in different genes, some genes or groups of genes are recurrently mutated across multiple cancer types. The latter is the case for the SWI/SNF complex, which is mutated in >25% of human cancers, and as such it is the most recurrently mutated chromatin remodeling complex across all cancer types[18][19]. In particular, SWI/SNF subunits such as ARID1A and SMARCA4 are recurrently identified as pan-cancer drivers in next-generation sequencing studies in thousands of patients[20][21]. However, other SWI/SNF subunits are preferentially mutated in specific tumors. Mutations in SWI/SNF subunits are usually loss-of-function and they often involve single nucleotide substitutions or small insertions or deletions. However, certain SWI/SNF subunits can also be affected by large-scale deletions or translocations. 

The first evidence of an association between SWI/SNF and cancer was discovered in rhabdoid tumors, which are rare pediatric tumors that are almost exclusively mutated (by point mutations, small indels, or large deletions) in the SWI/SNF subunit SMARCB1[22]. Later studies revealed other SWI/SNF subunits that are recurrently mutated in other cancer types. In lung adenocarcinoma (LUAD), we discovered that SMARCA4 is recurrently mutated in more than 10% of the patients (manuscript under submission) and 40% of cell lines[23]. In renal cell clear cell carcinoma, up to 41% of the cases harbor mutations or loss of PBRM1[24]. In diffuse large B-cell lymphoma and other B cell hematological malignancies, BCL7A is recurrently mutated, especially at its first splice donor site[25]. Overall, the diversity and recurrence of mutations in SWI/SNF subunits in cancer reflect the central role of SWI/SNF complexes in cells as well as their tissue-specific or context-dependent composition and function.

 

2.2.2. Translocations

Chromosomal translocations are large-scale rearrangements that frequently occur in certain cancers. Translocations can have various effects, such as the fusion of two or more distant protein- coding genes, leading to an aberrant fusion protein, or the fusion of a promoter and a cancer gene, resulting in an aberrant control of the transcription of the gene. Translocations that affect SWI/SNF genes are highly recurrent in certain cancers. For example, a hallmark of synovial sarcoma is a t(X;18) translocation that involves the SS18 gene and which creates a SS18-SSX fusion protein[26]. In addition, certain aggressive chronic lymphocytic leukemias harbor a t(2;14)(p13;q32.3) translocation that results in the BCL11A locus being under transcriptional control of regulatory elements from the IGH locus, leading to aberrant overexpression of BCL11A[27].

 

2.2.3. Epigenetic silencing and non-coding RNAs

SWI/SNF subunits can be aberrantly expressed in cancer in the absence of mutations in their genes. Recently, we reported that the mRNAs of all SWI/SNF subunits are recurrently downregulated in LUAD compared to matched normal lung tissue, and only a small proportion of the cases of downregulation could be explained by the presence of mutations in SWI/SNF genes (manuscript under submission). Similar observations were made for the protein levels of SMARCA4 and SMARCA2 measured by immunohistochemistry[28]. There may be multiple causes for the downregulation of SWI/SNF subunits in LUAD, including promoter hypermethylation and regulation by non-coding RNAs. For example, SMARCA2 is downregulated in some LUAD samples as a consequence of promoter hypermethylation[29]. In squamous cell carcinomas of various tissues, ARID1A is recurrently downregulated as a consequence of promoter hypermethylation[30]. In primary cutaneous T cell lymphoma, BCL7A is often epigenetically silenced by promoter hypermethylation[31]. In rhabdoid tumors and small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), SMARCA2 is either epigenetically silenced or transcriptionally inactive[32].

Regarding the regulation of the expression of SWI/SNF subunits by non-coding RNAs, we reported that hsa-miR-155 modulates SMARCA4 in LUAD[33]. In addition, in various tumor types, SMARCA2 expression is modulated by hsa-miR-199a-5p and -3p[34]. In colorectal carcinoma, SMARCC1 has an oncogenic role and it is a direct target of hsa-miR-202-5p, a tumor suppressor microRNA[35]. In turn, the SWI/SNF complex can also modulate the expression of cancer-related microRNAs. In lung adenocarcinoma, SMARCA4-containing SWI/SNF complexes control the expression of hsa-miR-222, which contributes to a tumor suppressor phenotype (manuscript under submission).

Importantly, changes in the expression of certain SWI/SNF subunits are associated with patient survival in certain tumor types. For example, in squamous cell carcinomas and cervical cancer, low expression of ARID1A is associated with poor prognosis[36]. In hepatocellular carcinoma, low expression of SMARCA2 is associated with poor survival[37]. However, in other cases, low expression of SWI/SNF subunits may be associated with a better prognosis. This is the case of SMARCA4 and ARID1A in breast cancer and bladder cancer[38][39]. Finally, high SMARCA4 expression is associated with unfavourable prognosis in hepatocellular carcinoma[40].

 

3. Therapeutic strategies

SWI/SNF alterations in tumors are usually loss-of-function. Because of the functional redundancy of certain SWI/SNF subunits, when one subunit is inactivated, it can often be partially or totally replaced by a paralog subunit. Therefore, the functional effect of the inactivation of SWI/SNF subunits is usually not a complete loss of function of the complex, but an aberrant activity as a result of alternative residual SWI/SNF complexes[41]. This situation can lead to synthetic lethalities: if SWI/SNF subunits “X” and “Y” are partly or completely interchangeable, and a tumor has inactivated “X”, then pharmacological inhibition of “Y” can lead to tumor regression. On the other hand, in cells that are wild type for “X”, inhibition of “Y” should not have such a strong functional effect because “X” can replace the function of “Y”. Therefore, synthetic lethalities open the possibility of tumor-specific therapies. Synthetic lethalities have also been observed between pairs of non-paralog SWI/SNF subunits. For example, SMARCB1-mutant cell lines have an increased dependence on the non-paralogous subunit BRD9[42]. In any case, because SWI/SNF aberrations are highly context-dependent, further studies are required to prove that cancers that lack one subunit are dependent on its paralog and that they have not evolved to become paralog-independent. However, even if a tumor becomes paralog-independent, other functional dependencies may arise. For example, lung and ovarian cancers lacking both ATPase subunits of the SWI/SNF become sensitive to bromodomain inhibitors[43].

Synthetic lethalities can also arise between SWI/SNF and non-SWI/SNF genes. For example, certain SWI/SNF mutant cancers are sensitive to inhibition of EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2)[44]. Further dependencies can be assessed using drug screens coupled with functional genomic depletion screens. One of such screens was performed in rhabdoid tumors, SCCOHT, and non-small cell lung carcinoma cell lines, and it identified that depletion of SWI/SNF genes leads to sensitivity to inhibitors of cell cycle regulators such as cyclin-dependent kinase 4 or 6 (CDK4/6) and Aurora A[45][46][47][48]. In another screen, rhabdoid tumors and ARID1A-mutant ovarian clear cell carcinomas were found to be dependent on several receptor tyrosine kinases, including platelet-derived growth factor receptors, FGFR1, and MET[49][50][51]. Finally, loss of PBRM1 expression may improve the response to immune checkpoint inhibitors because of transcriptional changes in genes from immune signaling pathways, such as JAK-STAT[52].

In conclusion, SWI/SNF subunits are especially attractive as therapeutic targets in the context of synthetic lethalities. Finding the correct inhibitors for specific contexts and tumor types may lead to highly specific and effective cancer therapies.

References

  1. Xiaomin Bao; Adam J. Rubin; Kun Qu; Jiajing Zhang; Paul G. Giresi; Howard Y. Chang; Paul A. Khavari; A novel ATAC-seq approach reveals lineage-specific reinforcement of the open chromatin landscape via cooperation between BAF and p63. Genome Biology 2015, 16, 1-17, 10.1186/s13059-015-0840-9.
  2. Hyockman Kwon; Anthony N. Imbalzano; Paul A. Khavari; Robert E. Kingston; Michael R. Green; Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex. Nature 1994, 370, 477-481, 10.1038/370477a0.
  3. Michael Stern; Robert Jensen; Ira Herskowitz; Five SWI genes are required for expression of the HO gene in yeast. Journal of Molecular Biology 1984, 178, 853-868, 10.1016/0022-2836(84)90315-2.
  4. Lenore Neigeborn; Marian Carlson; Genes Affecting the Regulation of SUC2 Gene Expression by Glucose Repression in SACCHAROMYCES CEREVISIAE. Genetics 1984, 108, 845-858.
  5. Richard C. Centore; Gabriel J. Sandoval; Luis Miguel Mendes Soares; Cigall Kadoch; Ho Man Chan; Mammalian SWI/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic Strategies. Trends in Genetics 2020, 36, 936-950, 10.1016/j.tig.2020.07.011.
  6. Jessica Ryme; Patrik Asp; Stefanie Böhm; Erica Cavellán; Ann-Kristin Östlund Farrants; Variations in the composition of mammalian SWI/SNF chromatin remodelling complexes. Journal of Cellular Biochemistry 2009, 108, 565-576, 10.1002/jcb.22288.
  7. Shilpa Kadam; Beverly M Emerson; Transcriptional Specificity of Human SWI/SNF BRG1 and BRM Chromatin Remodeling Complexes. Molecular Cell 2003, 11, 377-389, 10.1016/s1097-2765(03)00034-0.
  8. Cedric R. Clapier; Janet Iwasa; Cedric R. Clapier Bradley R. Cairns; Craig L. Peterson; Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nature Reviews Molecular Cell Biology 2017, 18, 407-422, 10.1038/nrm.2017.26.
  9. Gangqing Hu; Dustin E. Schones; Kairong Cui; River Ybarra; Daniel Northrup; Qingsong Tang; Luca Gattinoni; Nicholas P. Restifo; Suming Huang; Keji Zhao; et al. Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1. Genome Research 2011, 21, 1650-1658, 10.1101/gr.121145.111.
  10. Wenjing Qi; Ruoxi Wang; Hongyu Chen; Xiaolin Wang; Wang Xiaolin; Istvan Boldogh; Xueqing Ba; Liping Han; Xianlu Zeng; BRG1 promotes the repair of DNA double-strand breaks by facilitating the replacement of RPA with RAD51. Journal of Cell Science 2014, 128, 317-330, 10.1242/jcs.159103.
  11. Han-Sae Lee; Ji-Hye Park; So-Jung Kim; Su-Jung Kwon; Jongbum Kwon; A cooperative activation loop among SWI/SNF, γ-H2AX and H3 acetylation for DNA double-strand break repair. The EMBO Journal 2010, 29, 1434-1445, 10.1038/emboj.2010.27.
  12. Guang Peng; Eun-Kyoung Yim; Hui Dai; Andrew P. Jackson; Ineke Van Der Burgt; Mei-Ren Pan; Ruozhen Hu; Kaiyi Li; Shiaw-Yih Lin; BRIT1/MCPH1 links chromatin remodelling to DNA damage response. Nature 2009, 11, 865-872, 10.1038/ncb1895.
  13. Ghia M. Euskirchen; Raymond K. Auerbach; Eugene Davidov; Tara A. Gianoulis; Guoneng Zhong; Joel Rozowsky; Nitin Bhardwaj; Mark B. Gerstein; Michael Snyder; Diverse Roles and Interactions of the SWI/SNF Chromatin Remodeling Complex Revealed Using Global Approaches. PLOS Genetics 2011, 7, e1002008, 10.1371/journal.pgen.1002008.
  14. Radhika Mathur; Charles W.M. Roberts; SWI/SNF (BAF) Complexes: Guardians of the Epigenome. Annual Review of Cancer Biology 2018, 2, 413-427, 10.1146/annurev-cancerbio-030617-050151.
  15. Esther Y. Son; Gerald R. Crabtree; The role of BAF (mSWI/SNF) complexes in mammalian neural development. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 2014, 166, 333-349, 10.1002/ajmg.c.31416.
  16. Yoshinori Tsurusaki; Nobuhiko Okamoto; Hirofumi Ohashi; Tomoki Kosho; Yoko Imai; Yumiko Hibi-Ko; Tadashi Kaname; Kenji Naritomi; Hiroshi Kawame; Keiko Wakui; et al.Yoshimitsu FukushimaTomomi HommaMitsuhiro KatoYoko HirakiTakanori YamagataShoji YanoSeiji MizunoSatoru SakazumeTakuma IshiiToshiro NagaiMasaaki ShiinaKazuhiro OgataTohru OhtaNorio NiikawaSatoko MiyatakeIppei OkadaTakeshi MizuguchiHiroshi DoiHirotomo SaitsuNoriko MiyakeNaomichi Matsumoto Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nature Genetics 2012, 44, 376-378, 10.1038/ng.2219.
  17. Jeroen K J Van Houdt; Beata Anna Nowakowska; Sérgio B Sousa; Barbera D C Van Schaik; Eve Seuntjens; Nelson Avonce; Alejandro Sifrim; Omar A Abdul-Rahman; Marie-José H Van Den Boogaard; Armand Bottani; et al.Marco CastoriValérie Cormier-DaireMatthew A DeardorffIsabel FilgesAlan FryerJean-Pierre FrynsSimone GanaLivia GaravelliGabriele Gillessen-KaesbachBryan D HallDenise HornDanny HuylebroeckJakub KlapeckiMalgorzata Krajewska-WalasekAlma KuechlerMatthew A LinesSaskia M MaasKay D MacDermotShane McKeeAlex MageeStella A De ManYves MoreauFanny Morice-PicardEwa ObersztynJacek PilchElizabeth RosserNora ShannonIrene Stolte-DijkstraPatrick Van DijckCatheline VilainAnnick VogelsEmma WakelingDagmar WieczorekLouise C WilsonOrsetta ZuffardiAntoine H C Van KampenKoenraad DevriendtRaoul C M HennekamJoris Robert Vermeesch Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nature Genetics 2012, 44, 445-449, 10.1038/ng.1105.
  18. Cigall Kadoch; Diana C. Hargreaves; Courtney Hodges; Laura Elias; Lena Ho; Jeffrey A Ranish; Gerald R. Crabtree; Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nature Genetics 2013, 45, 592-601, 10.1038/ng.2628.
  19. A. Hunter Shain; Jonathan R. Pollack; The Spectrum of SWI/SNF Mutations, Ubiquitous in Human Cancers. PLOS ONE 2013, 8, e55119, 10.1371/journal.pone.0055119.
  20. Matthew H. Bailey; Collin Tokheim; Eduard Porta-Pardo; Sohini Sengupta; Denis Bertrand; Amila Weerasinghe; Antonio Colaprico; Michael C. Wendl; Jaegil Kim; Brendan Reardon; et al.Patrick Kwok-Shing NgKang Jin JeongSong CaoZixing WangJianjiong GaoQingsong GaoFang WangEric Minwei LiuLoris MularoniCarlota Rubio-PerezNiranjan NagarajanIsidro Cortés-CirianoDaniel Cui ZhouWen-Wei LiangJulian M. HessVenkata D. YellapantulaDavid TamboreroAbel Gonzalez-PerezChayaporn SuphavilaiJia Yu KoEkta KhuranaPeter J. ParkEliezer M. Van AllenHan LiangMichael S. LawrenceAdam GodzikNuria Lopez-BigasJosh StuartDavid WheelerGad GetzKen ChenAlexander J. LazarGordon B. MillsRachel KarchinLi DingSamantha J. Caesar-JohnsonJohn A. DemchokIna FelauMelpomeni KasapiMartin L. FergusonCarolyn M. HutterHeidi J. SofiaRoy TarnuzzerZhining WangLiming YangJean C. ZenklusenJiashan (Julia) ZhangSudha ChudamaniJia LiuLaxmi LollaRashi NareshTodd PihlQiang SunYunhu WanYe WuJuok ChoTimothy DeFreitasScott FrazerNils GehlenborgDavid I. HeimanPei LinSam MeierMichael S. NobleGordon SaksenaDoug VoetHailei ZhangBrady BernardNyasha ChambweVarsha DhankaniTheo KnijnenburgRoger KramerKalle LeinonenYuexin LiuMichael MillerSheila ReynoldsIlya ShmulevichVesteinn ThorssonWei ZhangRehan AkbaniBradley M. BroomApurva M. HegdeZhenlin JuRupa S. KanchiAnil KorkutJun LiShiyun LingWenbin LiuYiling LuKwok-Shing NgArvind RaoMichael RyanJing WangJohn N. WeinsteinJiexin ZhangAdam AbeshouseJoshua ArmeniaDebyani ChakravartyWalid K. ChatilaIno De BruijnBenjamin E. GrossZachary J. HeinsRitika KundraKonnor LaMarc LadanyiAugustin LunaMoriah G. NissanAngelica OchoaSarah M. PhillipsEd ReznikFrancisco Sanchez-VegaChris SanderNikolaus SchultzRobert SheridanS. Onur SumerYichao SunBarry S. TaylorJioajiao WangHongxin ZhangPavana AnurMyron PetoPaul SpellmanChristopher BenzJoshua M. StuartChristopher K. WongChristina YauD. Neil HayesJoel S. ParkerMatthew D. WilkersonAdrian AllyMiruna BalasundaramReanne BowlbyDenise BrooksRebecca CarlsenEric ChuahNoreen DhallaRobert HoltSteven J.M. JonesKatayoon KasaianDarlene LeeYussanne MaMarco A. MarraMichael MayoRichard A. MooreAndrew J. MungallKaren MungallA. Gordon RobertsonSara SadeghiJacqueline E. ScheinPayal SipahimalaniAngela TamNina ThiessenKane TseTina WongAshton C. BergerRameen BeroukhimAndrew D. CherniackCarrie CibulskisStacey B. GabrielGalen F. GaoGavin HaMatthew MeyersonSteven E. SchumacherJuliann ShihMelanie H. KucherlapatiRaju S. KucherlapatiStephen BaylinLeslie CopeLudmila DanilovaMoiz S. BootwallaPhillip H. LaiDennis T. MaglinteDavid J. Van Den BergDaniel J. WeisenbergerJ. Todd AumanSaianand BaluTom BodenheimerCheng FanKatherine A. HoadleyAlan P. HoyleStuart R. JefferysCorbin D. JonesShaowu MengPiotr A. MieczkowskiLisle E. MoseAmy H. PerouCharles M. PerouJeffrey RoachYan ShiJanae V. SimonsTara SkellyMatthew G. SolowayDonghui TanUmadevi VeluvoluHuihui FanToshinori HinouePeter W. LairdHui ShenWanding ZhouMichelle BellairKyle ChangKyle CovingtonChad J. CreightonHuyen DinhHarshavardhan DoddapaneniLawrence A. DonehowerJennifer DrummondRichard A. GibbsRobert GlennWalker HaleYi HanJianhong HuViktoriya KorchinaSandra LeeLora LewisWei LiXiuping LiuMargaret MorganDonna MortonDonna MuznyJireh SantibanezMargi ShethEve ShinbrotLinghua WangMin WangLiu XiFengmei ZhaoElizabeth L. AppelbaumMatthew G. CordesCatrina C. FronickLucinda A. FultonRobert S. FultonCyriac KandothElaine R. MardisMichael D. McLellanChristopher A. MillerHeather K. SchmidtRichard K. WilsonDaniel CrainErin CurleyJohanna GardnerKevin LauDavid MalleryScott MorrisJoseph PaulauskisRobert PennyCandace SheltonTroy SheltonMark ShermanEric ThompsonPeggy YenaJay BowenJulie M. Gastier-FosterMark GerkenKristen M. LeraasTara M. LichtenbergNilsa C. RamirezLisa WiseErik ZmudaNiall CorcoranTony CostelloChristopher HovensAndre L. CarvalhoAna C. De CarvalhoJosé H. FregnaniAdhemar Longatto-FilhoRui M. ReisCristovam Scapulatempo-NetoHenrique C.S. SilveiraDaniel O. VidalAndrew BurnetteJennifer EschbacherBeth HermesArdene NossRosy SinghMatthew L. AndersonPatricia D. CastroMichael IttmannDavid HuntsmanBernard KohlXuan LeRichard ThorpChris AndryElizabeth R. DuffyVladimir LyadovOxana PaklinaGaliya SetdikovaAlexey ShabuninMikhail TavobilovChristopher McPhersonRonald WarnickRoss BerkowitzDaniel CramerColleen FeltmateNeil HorowitzAdam KibelMichael MutoChandrajit P. RautAndrei MalykhJill S. Barnholtz-SloanWendi BarrettKaren DevineJordonna FulopQuinn T. OstromKristen ShimmelYingli WolinskyAndrew E. SloanAgostino De RoseFelice GiulianteMarc GoodmanBeth Y. KarlanCurt H. HagedornJohn EckmanJodi HarrJerome MyersKelinda TuckerLeigh Anne ZachBrenda DeyarminHai HuLeonid KvecherCaroline LarsonRichard J. MuralStella Somiari Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell 2018, 174, 1034-1035, 10.1016/j.cell.2018.07.034.
  21. The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium; Pan-cancer analysis of whole genomes. Nature 2020, 578, 82-93, 10.1038/s41586-020-1969-6.
  22. Isabella Versteege; Nicolas Sévenet; Julian Lange; Marie-Françoise Rousseau-Merck; Peter Ambros; Rupert Handgretinger; Alain Aurias; Olivier Delattre; Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 1998, 394, 203-206, 10.1038/28212.
  23. Paola Peinado; Alvaro Andrades; Marta Cuadros; Maria Isabel Rodriguez; Isabel F. Coira; Daniel J. Garcia; Juan Carlos Álvarez-Perez; Carlos Baliñas-Gavira; Alberto M. Arenas; Juan Rodrigo Patiño-Mercau; et al.Juan Sanjuan-HidalgoOctavio A. RomeroLuis M. MontuengaJulian CarreteroMontserrat Sanchez-CespedesPedro P. Medina Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models. Cancers 2020, 12, 3712, 10.3390/cancers12123712.
  24. Ignacio Varela; Patrick Tarpey; Keiran Raine; Dachuan Huang; Choon Kiat Ong; Philip Stephens; Helen Davies; David Jones; Meng-Lay Lin; Jon Teague; et al.Graham BignellAdam ButlerJuok ChoGillian L. DalglieshDanushka GalappaththigeChris GreenmanClaire HardyMingming JiaCalli LatimerKing Wai LauJohn MarshallStuart McLarenAndrew MenziesLaura MudieLucy StebbingsDavid A. LargaespadaL. F. A. WesselsStephane RichardRichard J. KahnoskiJohn AnemaDavid A. TuvesonPedro A. Perez-ManceraVille MustonenAndrej FischerDavid J. AdamsAlistair RustWaraporn Chan-OnChutima SubimerbKarl DykemaKyle FurgePeter J. CampbellBin Tean TehMichael R. StrattonP. Andrew Futreal Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 2011, 469, 539-542, 10.1038/nature09639.
  25. Carlos Baliñas-Gavira; María I. Rodríguez; Alvaro Andrades; Marta Cuadros; Juan Carlos Álvarez-Pérez; Ángel F. Álvarez-Prado; Virginia G. De Yébenes; Sabina Sánchez-Hernández; Elvira Fernández-Vigo; Javier Muñoz; et al.Francisco MartínAlmudena R. RamiroJosé A. Martínez-ClimentPedro P. Medina Frequent mutations in the amino-terminal domain of BCL7A impair its tumor suppressor role in DLBCL. Leukemia 2020, 34, 2722-2735, 10.1038/s41375-020-0919-5.
  26. Norifumi Naka; Satoshi Takenaka; Nobuhito Araki; Toshitada Miwa; Nobuyuki Hashimoto; Kiyoko Yoshioka; Susumu Joyama; Ken-Ichiro Hamada; Yoshitane Tsukamoto; Yasuhiko Tomita; et al.Takafumi UedaHideki YoshikawaKazuyuki Itoh Synovial Sarcoma is a Stem Cell Malignancy. STEM CELLS 2010, 28, 1119-1131, 10.1002/stem.452.
  27. Ed Satterwhite; Takashi Sonoki; Tony G. Willis; Lana Harder; Rachael Nowak; Emma L. Arriola; Hui Liu; Helen P. Price; Stefan Gesk; Doris Steinemann; et al.Brigitte SchlegelbergerDavid G. OscierReiner SiebertPhilip W. TuckerMartin J. S. Dyer The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. Blood 2001, 98, 3413-3420, 10.1182/blood.v98.12.3413.
  28. David N Reisman; Janiece Sciarrotta; Weidong Wang; William K Funkhouser; Bernard E Weissman; Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis.. Cancer Research 2003, 63, 560-566 .
  29. Jixiang Wu; Keshuai He; Yajun Zhang; Jixiang Song; Zhan Shi; Weiwei Chen; Yongfeng Shao; Inactivation of SMARCA2 by promoter hypermethylation drives lung cancer development. Gene 2019, 687, 193-199, 10.1016/j.gene.2018.11.032.
  30. Qingyu Luo; Xiaowei Wu; Wan Chang; Pengfei Zhao; Xiaolin Zhu; Hongyan Chen; Yabing Nan; Aiping Luo; Xuantong Zhou; Dan Su; et al.Wenjie JiaoZhihua Liu ARID1A Hypermethylation Disrupts Transcriptional Homeostasis to Promote Squamous Cell Carcinoma Progression.. null 2020, 80, 406-417.
  31. Remco Van Doorn; Willem H. Zoutman; Remco Dijkman; Renee X. De Menezes; Suzan Commandeur; Aat A. Mulder; Pieter A. Van Der Velden; Maarten H. Vermeer; Rein Willemze; Pearlly S. Yan; et al.Tim H. HuangCornelis P. Tensen Epigenetic Profiling of Cutaneous T-Cell Lymphoma: Promoter Hypermethylation of Multiple Tumor Suppressor Genes Including BCL7a, PTPRG, and p73. Journal of Clinical Oncology 2005, 23, 3886-3896, 10.1200/jco.2005.11.353.
  32. Anthony N. Karnezis; Yemin Wang; Pilar Ramos; William P.D. Hendricks; Esther Oliva; Emanuela D'angelo; Jaime Prat; Marisa R. Nucci; Torsten O. Nielsen; Christine Chow; et al.Samuel LeungFriedrich KommossStefan KommossAnnacarolina SilvaBrigitte M. RonnettJoseph T. RabbanDavid D. BowtellBernard E. WeissmanJeffrey M. TrentC. Blake GilksDavid G. Huntsman Dual loss of the SWI / SNF complex ATPases SMARCA4 / BRG1 and SMARCA2 / BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type. The Journal of Pathology 2015, 238, 389-400, 10.1002/path.4633.
  33. Isabel F. Coira; Eva E. Rufino-Palomares; Octavio A. Romero; Paola Peinado; Chanatip Metheetrairut; Laura Boyero-Corral; Julian Carretero; Esther Farez-Vidal; Marta Cuadros; Fernando J. Reyes-Zurita; et al.Jose A. LupiáñezMontse Sánchez-CespedesFrank J. SlackPedro P. Medina Expression inactivation of SMARCA4 by microRNAs in lung tumors. Human Molecular Genetics 2014, 24, 1400-1409, 10.1093/hmg/ddu554.
  34. Kouhei Sakurai; Chihiro Furukawa; Takeshi Haraguchi; Ken-Ichi Inada; Kazuya Shiogama; Takanobu Tagawa; Shuji Fujita; Yoshihito Ueno; Aya Ogata; Mai Ito; et al.Yutaka TsutsumiHideo Iba MicroRNAs miR-199a-5p and -3p Target the Brm Subunit of SWI/SNF to Generate a Double-Negative Feedback Loop in a Variety of Human Cancers. Cancer Research 2010, 71, 1680-1689, 10.1158/0008-5472.can-10-2345.
  35. Shao-Bo Ke; Hu Qiu; Jia-Mei Chen; Wei Shi; Yong-Shun Chen; MicroRNA-202-5p functions as a tumor suppressor in colorectal carcinoma by directly targeting SMARCC1. Gene 2018, 676, 329-335, 10.1016/j.gene.2018.08.064.
  36. Hanbyoul Cho; Jane Seon-Young Kim; Hyunsoo Chung; Candice Perry; Heejeong Lee; Jae-Hoon Kim; Loss of ARID1A/BAF250a expression is linked to tumor progression and adverse prognosis in cervical cancer. Human Pathology 2013, 44, 1365-1374, 10.1016/j.humpath.2012.11.007.
  37. Mio Endo; Kohichiroh Yasui; Yoh Zen; Yasuyuki Gen; Keika Zen; Kazuhiro Tsuji; Osamu Dohi; Hironori Mitsuyoshi; Shinji Tanaka; Masafumi Taniwaki; et al.Yasuni NakanumaShigeki AriiToshikazu Yoshikawa Alterations of the SWI/SNF chromatin remodelling subunit-BRG1 and BRM in hepatocellular carcinoma. Liver International 2012, 33, 105-117, 10.1111/liv.12005.
  38. Jin Bai; Pengjin Mei; Cuipeng Zhang; Feifei Chen; Chen Li; Zhenqiang Pan; Hui Liu; Junnian Zheng; BRG1 Is a Prognostic Marker and Potential Therapeutic Target in Human Breast Cancer. PLOS ONE 2013, 8, e59772, 10.1371/journal.pone.0059772.
  39. Sheila F. Faraj; Alcides Chaux; Nilda Gonzalez-Roibon; Enrico Munari; Carla Ellis; Tina Driscoll; Mark P. Schoenberg; Trinity J. Bivalacqua; Ie-Ming Shih; George J. Netto; et al. ARID1A immunohistochemistry improves outcome prediction in invasive urothelial carcinoma of urinary bladder. Human Pathology 2014, 45, 2233-2239, 10.1016/j.humpath.2014.07.003.
  40. Benedikt Kaufmann; Baocai Wang; Suyang Zhong; Melanie Laschinger; Pranali Patil; Miao Lu; Volker Assfalg; Zhangjun Cheng; Helmut Friess; Norbert Hüser; et al.Guido Von FiguraDaniel Hartmann BRG1 promotes hepatocarcinogenesis by regulating proliferation and invasiveness. PLOS ONE 2017, 12, e0180225, 10.1371/journal.pone.0180225.
  41. Priya Mittal; Charles W. M. Roberts; The SWI/SNF complex in cancer — biology, biomarkers and therapy. Nature Reviews Clinical Oncology 2020, 17, 435-448, 10.1038/s41571-020-0357-3.
  42. Brittany C. Michel; Andrew R. D’Avino; Seth H. Cassel; Nazar Mashtalir; Zachary M. McKenzie; Matthew J. McBride; Alfredo M. Valencia; Qianhe Zhou; Michael Bocker; Luis M. M. Soares; et al.Joshua PanDavid I. RemillardCaleb A. LareauHayley J. ZullowNora FortoulNathanael S. GrayJames E. BradnerHo Man ChanCigall Kadoch A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nature 2018, 20, 1410-1420, 10.1038/s41556-018-0221-1.
  43. Tatiana Shorstova; Maud Marques; Jie Su; Jake Johnston; Claudia L. Kleinman; Nancy Hamel; Sidong Huang; Moulay A. Alaoui-Jamali; William D. Foulkes; Michael Witcher; et al. SWI/SNF-Compromised Cancers Are Susceptible to Bromodomain Inhibitors. Cancer Research 2019, 79, 2761-2774, 10.1158/0008-5472.can-18-1545.
  44. Kimberly H. Kim; Woojin Kim; Thomas P. Howard; Francisca Vazquez; Aviad Tsherniak; Jennifer N. Wu; Weishan Wang; Jeffrey R. Haswell; Loren D. Walensky; William C. Hahn; et al.Stuart H. OrkinCharles W. M. Roberts SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2. Nature Medicine 2015, 21, 1491-1496, 10.1038/nm.3968.
  45. Vural Tagal; Shuguang Wei; Wei Zhang; Rolf A. Brekken; Bruce A. Posner; Michael Peyton; Luc Girard; Taehyun Hwang; David A. Wheeler; John D. Minna; et al.Michael A. WhiteAdi F. GazdarMichael G. Roth SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers. Nature Communications 2017, 8, 14098, 10.1038/ncomms14098.
  46. Yibo Xue; Brian Meehan; Elizabeth Macdonald; Sriram Venneti; Xue Qing D. Wang; Leora Witkowski; Petar Jelinic; Tim Kong; Daniel Martinez; Geneviève Morin; et al.Michelle FirlitAtefeh AbediniRadia M. JohnsonRegina CencicJay PatibandlaHongbo ChenAndreas I. PapadakisAurelie AugusteIris De RinkRon M. KerkhovenNicholas BertosWalter H. GotliebBlaise A. ClarkeAlexandra LearyMichael WitcherMarie-Christine GuiotJerry PelletierJosée DostieMorag ParkAlexander R. JudkinsRalf HassDouglas A. LevineJanusz RakBarbara VanderhydenWilliam D. FoulkesSidong Huang CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary. Nature Communications 2019, 10, 1-15, 10.1038/s41467-018-06958-9.
  47. Yibo Xue; Brian Meehan; Zheng Fu; Xue Qing D. Wang; Pierre Olivier Fiset; Ralf Rieker; Cameron Levins; Tim Kong; Xianbing Zhu; Geneviève Morin; et al.LaShanda SkerrittEsther HerpelSriram VennetiDaniel MartinezAlexander R. JudkinsSungmi JungSophie Camilleri-BroetAnne V. GonzalezMarie-Christine GuiotWilliam W. LockwoodJonathan D. SpicerAbbas AgaimyWilliam A. PastorJosée DostieJanusz RakWilliam D. FoulkesSidong Huang SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in non-small cell lung cancer. Nature Communications 2019, 10, 1-13, 10.1038/s41467-019-08380-1.
  48. Sujatha Venkataraman; Irina Alimova; Tiffany Tello; Peter S. Harris; Jeffrey A. Knipstein; Andrew M. Donson; Nicholas K. Foreman; Arthur K. Liu; Rajeev Vibhakar; Targeting Aurora Kinase A enhances radiation sensitivity of atypical teratoid rhabdoid tumor cells. Journal of Neuro-Oncology 2012, 107, 517-526, 10.1007/s11060-011-0795-y.
  49. Jocelyn P. Wong; Jason R. Todd; Martina A. Finetti; Frank McCarthy; Malgorzata Broncel; Simon Vyse; Maciej T. Luczynski; Stephen Crosier; Karen A. Ryall; Kate Holmes; et al.Leo S. PayneFrances DaleyPatty WaiAndrew JenksBarbara TanosAik-Choon TanRachael C. NatrajanDaniel WilliamsonPaul H. Huang Dual Targeting of PDGFRα and FGFR1 Displays Synergistic Efficacy in Malignant Rhabdoid Tumors. Cell Reports 2016, 17, 1265-1275, 10.1016/j.celrep.2016.10.005.
  50. Rowan E. Miller; Rachel Brough; Ilirjana Bajrami; Chris T. Williamson; Simon McDade; James Campbell; Asha Kigozi; Rumana Rafiq; Helen Pemberton; Rachel Natrajan; et al.Josephine JoelHolly AstleyClaire MahoneyJonathan D. MooreChris TorranceJohn D. GordanJames T. WebberRebecca S. LevinKevan M. ShokatSourav BandyopadhyayChristopher J. LordAlan Ashworth Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib. Molecular Cancer Therapeutics 2016, 15, 1472-1484, 10.1158/1535-7163.mct-15-0554.
  51. Elaine M. Oberlick; Matthew G. Rees; Brinton Seashore-Ludlow; Francisca Vazquez; Geoffrey M. Nelson; Neekesh V. Dharia; Barbara A. Weir; Aviad Tsherniak; Mahmoud Ghandi; John M. Krill-Burger; et al.Robin M. MeyersXiaofeng WangPhil MontgomeryDavid E. RootJake M. BieberSandi RadkoJaime H. CheahC. Suk-Yee HonAlykhan F. ShamjiPaul A. ClemonsPeter J. ParkMichael A. DyerTodd R. GolubKimberly StegmaierWilliam C. HahnElizabeth A. StewartStuart L. SchreiberCharles W.M. Roberts Small-Molecule and CRISPR Screening Converge to Reveal Receptor Tyrosine Kinase Dependencies in Pediatric Rhabdoid Tumors. Cell Reports 2019, 28, 2331-2344.e8, 10.1016/j.celrep.2019.07.021.
  52. Diana Miao; Claire A. Margolis; Wenhua Gao; Martin H. Voss; William G Kaelin; Dylan J. Martini; Craig Norton; Dominick Bossé; Stephanie M. Wankowicz; Dana Cullen; et al.Christine HorakMegan Wind-RotoloAdam TracyMarios GiannakisFrank Stephen HodiCharles G. DrakeMark W. BallMohamad E. AllafAlexandra SnyderMatthew D. HellmannThai HoRobert J. MotzerSabina SignorettiWilliam G. Kaelin Jr.Toni K. ChoueiriEliezer M. Van Allen Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science 2018, 359, 801-806, 10.1126/science.aan5951.
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