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Lui, V.C.H.;  Ye, Y.;  Tam, P.K.H. Pathogenesis of Choledochal Cyst. Encyclopedia. Available online: (accessed on 23 April 2024).
Lui VCH,  Ye Y,  Tam PKH. Pathogenesis of Choledochal Cyst. Encyclopedia. Available at: Accessed April 23, 2024.
Lui, Vincent Chi Hang, Yongqin Ye, Paul Kwong Hang Tam. "Pathogenesis of Choledochal Cyst" Encyclopedia, (accessed April 23, 2024).
Lui, V.C.H.,  Ye, Y., & Tam, P.K.H. (2022, June 24). Pathogenesis of Choledochal Cyst. In Encyclopedia.
Lui, Vincent Chi Hang, et al. "Pathogenesis of Choledochal Cyst." Encyclopedia. Web. 24 June, 2022.
Pathogenesis of Choledochal Cyst

Choledochal cysts (CC) is characterized by extra- and/or intra-hepatic b\ile duct dilations. There are two main theories, “pancreaticobiliary maljunction” and “congenital stenosis of bile ducts” proposed for the pathogenesis of CC. Although family cases or CC associated with other anomalies have been reported, the molecular pathogenesis of CC is still poorly understood. Advances in transcriptomics and genomics analysis platforms have unveiled key expression signatures/genes/signaling pathways in the pathogenesis of human diseases including CC.

choledochal cyst pathogenesis genomics transcriptomics

1. Introduction

Choledochal cysts (CC), also known as congenital biliary dilation, presents as the dilation of extrahepatic bile ducts. It has a worldwide incidence of about 1:100,000 to 1:150,000 but the incidence can be as high as 1 in 1000 in Asians. In addition, the disease incidence shows a female predominance, with a female to male ratio of 3~4:1. CC is often seen in infants, and can be diagnosed incidentally or when it causes biliary pancreatitis with abdominal pain, jaundice, and even liver enlargement. According to Todani’s classification [1], CC can be anatomically classified into 5 major types (type I–V). Type I, a dilation of extrahepatic common biliary duct (CBD), and type IV, a dilation of both intrahepatic bile duct and extrahepatic CBD, are the two most common types, accounting for about 50–80% and 15–35% of all the CC cases, respectively. Type II, a diverticulum of CBD, and Type III, a dilation of the duodenal portion of the CBD that bulges into duodenal lumen, are rarely seen in infants. Type V, also called Caroli disease, is characterized by multiple dilations of the intrahepatic bile ducts, and the disease is always accompanied with polycystic kidney disease (PKD) or congenital liver fibrosis (Caroli syndrome).
The etiology of CC remains unclear. There are two main theories, “pancreaticobiliary maljunction” and “congenital stenosis of bile ducts”, proposed for the pathogenesis of CC [2][3][4][5]. Pancreaticobiliary maljunction is a congenital malformation in which the pancreatic and bile ducts join outside the duodenal wall, forming an abnormally long common channel. In patients with pancreaticobiliary maljunction, the sphincter of Oddi fails to regulate the function of the pancreaticobiliary junction, resulting in a two-way regurgitation and a mixing of pancreatic juice and bile, which activates the pancreatic enzymes in the pancreatic juice, leading to bile duct damages and inflammation, which subsequently result in a dilation of the bile duct as seen in CC. However, pancreaticobiliary maljunction can only be identified in about 50–80% of patients with CC [6]. Congenital stenosis of bile ducts is characterized by a reduced number of ganglions and neurons of the CBD, which causes a dysregulated contraction and increased intralumenal pressure in the proximal bile duct, leading to a cystic distention of the proximal CBD in CC [7][8][9][10].

2. Chromosomal Anomalies

Chromosomal anomalies have been identified in CC (Table 1). Chromosomal duplications such as 17q12 are seen in type Ia CC [11]. 17q12 chromosomal region contains the HNF1B gene, and HNF1B mutations or 17q12 microdeletions are usually seen in patients with nephritic cysts, diabetes syndrome, and neurologic and psychiatric symptoms [12][13][14][15][16][17]HNF1B encodes a transcription factor called hepatic nuclear factor-1 β (HNF1B), which is involved in bile duct organogenesis [18], and its deletion has been shown to induce jaundice, and anomalies of gall bladder [19]. Kettunen et al. evaluated 14 patients with HNF1B mutations and found 6 patients had CC, which exceeds the overall incidence of CC in the general population, indicating that mutations HNF1B in 17q12 may play a role in the pathogenesis of CC [20]. Later, Kotalova et al. reported that a two-week-old boy carrying a 17q12 duplication spanning 1698 kb that contains the HNF1B gene also suffered from CC, which is similar to the phenotype as seen in patients with a 17q12 microdeletion. The 17q12 duplication led to an overdosage of HNF1B and was found both in the young boy and his mother, indicating that the autosomal dominant inherence may exist, although his mother was completely within normal range [11].
Table 1. Chromosomal alterations reported in choledochal cyst patients.
Chromosomal Anomaly Localization Phenotype Description Type Candidate Gene References
Duplication 17q12 Diabetes, renal disorders, structural brain anomalies, etc. Ia HNF1B [11]
Deletion Microdeletion 17q12 Diabetes, renal cysts, neurological and psychological anomalies, biliary or hepatic clinical phenotype I, IV HNF1B [20]
Deletion 2p15p16.1 facial features, developmental delay Congenital microcephalyand intractable myoclonic epilepsy II EHBP1 [21]
Deletion 5q Familial adenomatous polyposis V - [22]
Translocation t(3;8)(p23;q13) Abdominal pain, jaundice V APC [23]
De novo 2p15p16.1 microdeletion encompassing the CCT4COMMD1B3GNT2, and EHBP1 genes has been shown to associate with multiple congenital anomalies including renal anomalies, intractable seizures, and a choledochal cyst [21][24][25][26][27][28][29]. Among these genes, EHBP1, the gene-encoding and actin-binding protein for cytophagy, was the only gene deleted in a type II CC patient [21]. Chromosome arm 5q deletion has been widely reported in familial adenomatous polyposis (FAP), which is due to mutations of the APC gene [30][31]. Deletion of chromosome 5q was once reported in a type V CC (Caroli disease) patient with FAP [22]. A cytogenetic study of a patient with a familial isolated Caroli disease revealed an unbalanced translocation between chromosome 3 and chromosome 8 with t(3;8) [23]. Genes located in 3p23 and 8q13 were rearranged, indicating that the distal loss and/or gain of 8q may contribute to the pathogenesis of Caroli disease. Genomic gains of 8q can promote ribosome biogenesis activity, which promotes hepatocellular carcinoma development [32][33]. CC has a higher risk of malignancy transformation [34][35][36], although a link between chromosomal translocation t(3;8) leading to a gain of 8q13-qter and the risk of malignancy transformation in CC has yet to be established.

3. Transcriptomics Analysis

There have been few microarray or RNA sequencing studies on the etiology of CC. Lv et al. performed transcriptome sequencing analysis on subtypes of Type I CC including cystic CC (Ia) and fusiform CC (Ic), and identified 6463 differentially expressed genes (DEGs) implicated in the biological processes of epithelial cell differentiation or extracellular matrix between these two CC subtypes [37]. Pathways related to metabolism and hormone regulation were enriched in cystic forms, while pathways related to immune response were enriched in fusiform CC [38][39]. An enrichment of immune-related genes is in line with a common clinical manifestation of immune-related complications including cholangitis and pancreatitis in fusiform CC [38][39]. Weighted gene co-expression network analysis (WGCNA) enables identification of gene modules and key genes that were correlated and relevant to clinical traits [40][41]. Using WGCNA, 12 co-expression modules were constructed, and the blue module, comprising the second most genes, was identified to be strongly correlated with fusiform CC [37], indicating that genes within this module could be potential markers for subtypes of CC. To further investigate key candidate genes in this module, a protein–protein interaction (PPI) was performed and found that the blue module contained key genes enriched in the Wnt signaling pathway, and activation of the Wnt pathway was associated with cholangio-carcinogenesis [42][43]. CC has a higher risk of malignancy transformation; whether an activation of Wnt pathway is involved in malignancy transformation of CC requires further investigation. ERBB2 and WNT11 were the two hub genes in this same module that distinguished fusiform CC and cystic CC. ERBB2 mutations/amplifications were implicated in extrahepatic cholangiocarcinoma [44][45][46]. All of these indicated that the CC subtypes share some common transcriptomic signatures, but each one also displays its own unique transcriptomic signatures. Therefore, elucidation of their common and unique transcriptomic signatures for each CC subtype will not only provide insights into the molecular pathogenesis of each subtype but also help in clinical management of the disease. For example, if the subtype’s unique transcriptomic signature suggests an elevated risk of cancer development, a more frequent follow-up and closer monitoring of any pre-malignant changes in the liver of post-surgical patients will help to identify patients for early cancer treatment.

4. Genetic Variants

A trio-based whole exome-sequencing of 31 CC trios was performed to identify de novo variants [47]. A total of 27 non-synonymous de novo variants were identified, 21 of which were damaging de novo variants, including 4 protein truncating mutations and 17 missense mutations. The constraint scores on average are statistically higher than random samples, indicating that these sequence variations are likely to contribute to CC. Six genes (PXDNRTEL1ANKRD11MAP2K1CYLD, and ACAN) with the de novo variants are involved in human developmental diseases, such as sclerocornea, spondyloepimetaphyseal dysplasia, dyskeratosis congenita, and familial multiple trichoepitheliomata [48][49][50][51][52][53][54][55][56]. Furthermore, four genes (PIK3CATLN1 CYLD, and MAP2K1) with the damaging variants are linked to bile duct and liver cancer. De novo variants in significantly mutated regions (SMRs) genes (PIK3CAC6, and PPP2R2B) were over-represented in CC patients, especially PIK3CA with excess mutations implicated in 9 cancer types, indicating that it may play a role in malignancy [57][58][59][60][61]. A total of 12 genes (DCHS1EPS15DNM1C5orf42POU2F2THBS1POU2F2BYSLC5orf42THBS1BYSLTXLNB) with de novo damaging variants recurrently identified in different individuals, forming either protein–protein interactions (PPIs) or compound heterozygotes or in homozygous. PPI pair TRIM28 and ZNF382 were overrepresented in CC group compared to controls in PPI analyses, with 3 and 2 patients carrying rare damaging variants on these two genes, respectively. TRIM28, known for regulation of the endoderm differentiation and involvement in malignancy, may play a role in CC [62][63][64][65]. Though the whole exome sequencing study was limited by a small sample size, CC is regarded as a multigenetic disease with mutations in more than one gene with genetic heterogeneity [47].


  1. Todani, T.; Watanabe, Y.; Narusue, M.; Tabuchi, K.; Okajima, K. Congenital bile duct cysts: Classification, operative procedures, and review of thirty-seven cases including cancer arising from choledochal cyst. Am. J. Surg. 1977, 134, 263–269.
  2. Makin, E.; Davenport, M. Understanding choledochal malformation. Arch. Dis. Child 2012, 97, 69–72.
  3. Kemmotsu, H.; Mouri, T.; Muraji, T. Congenital stenosis of the hepatic duct at the porta hepatis in children with choledochal cyst. J. Pediatr. Surg. 2009, 44, 512–516.
  4. Kato, T. Etiological relationships between choledochal cyst and anomalous junction of the pancreaticobiliary ductal system. Keio J. Med. 1989, 38, 136–151.
  5. Cao, J.; Wang, L.; Zou, X. Coexistence of Complete Pancreas Divisum and Anomalous Pancreaticobiliary Junction in a Patient with Type IA Choledochal Cyst. Clin. Gastroenterol. Hepatol. 2019, 17, A27–A28.
  6. Singham, J.; Yoshida, E.M.; Scudamore, C.H. Choledochal cysts: Part 1 of 3: Classification and pathogenesis. Can. J. Surg. 2009, 52, 434–440.
  7. Shimotake, T.; Iwai, N.; Yanagihara, J.; Inoue, K.; Fushiki, S. Innervation patterns in congenital biliary dilatation. Eur. J. Pediatr. Surg. 1995, 5, 265–270.
  8. Lewis, V.A.; Adam, S.Z.; Nikolaidis, P.; Wood, C.; Wu, J.G.; Yaghmai, V.; Miller, F.H. Imaging of choledochal cysts. Abdom. Imaging 2015, 40, 1567–1580.
  9. Kusunoki, M.; Yamamura, T.; Takahashi, T.; Kantoh, M.; Ishikawa, Y.; Utsunomiya, J. Choledochal cyst. Its possible autonomic involvement in the bile duct. Arch. Surg. 1987, 122, 997–1000.
  10. Davenport, M.; Basu, R. Under pressure: Choledochal malformation manometry. J. Pediatr. Surg. 2005, 40, 331–335.
  11. Kotalova, R.; Dusatkova, P.; Drabova, J.; Elblova, L.; Dedic, T.; Cinek, O.; Lebl, J.; Pruhova, S. Choledochal Cyst with 17q12 Chromosomal Duplication. Ann. Hum. Genet. 2018, 82, 48–51.
  12. Rogdaki, M.; Jauhar, S.; McCutcheon, R.; Howes, O. Treatment-Resistant Schizophrenia in a Patient With 17q12 Duplication. Biol. Psychiatry 2016, 80, e19–e20.
  13. Kamath, A.; Linden, S.C.; Evans, F.M.; Hall, J.; Jose, S.F.; Spillane, S.A.; Hardie, A.D.R.; Morgan, S.M.; Pilz, D.T. Chromosome 17q12 duplications: Further delineation of the range of psychiatric and clinical phenotypes. Am. J. Med. Genet. B Neuropsychiatry Genet. 2018, 177, 520–528.
  14. Hardies, K.; Weckhuysen, S.; Peeters, E.; Holmgren, P.; Van Esch, H.; De Jonghe, P.; Van Paesschen, W.; Suls, A. Duplications of 17q12 can cause familial fever-related epilepsy syndromes. Neurology 2013, 81, 1434–1440.
  15. Clissold, R.L.; Shaw-Smith, C.; Turnpenny, P.; Bunce, B.; Bockenhauer, D.; Kerecuk, L.; Waller, S.; Bowman, P.; Ford, T.; Ellard, S.; et al. Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. Kidney Int. 2016, 90, 203–211.
  16. Clissold, R.L.; Hamilton, A.J.; Hattersley, A.T.; Ellard, S.; Bingham, C. HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum. Nat. Rev. Nephrol. 2015, 11, 102–112.
  17. Calle Sánchez, X.; Helenius, D.; Bybjerg-Grauholm, J.; Pedersen, C.; Hougaard, D.M.; Børglum, A.D.; Nordentoft, M.; Mors, O.; Mortensen, P.B.; Geschwind, D.H.; et al. Comparing Copy Number Variations in a Danish Case Cohort of Individuals with Psychiatric Disorders. JAMA Psychiatry 2022, 79, 59–69.
  18. Strazzabosco, M.; Fabris, L. Development of the bile ducts: Essentials for the clinical hepatologist. J. Hepatol. 2012, 56, 1159–1170.
  19. Kotalova, R.; Dusatkova, P.; Cinek, O.; Dusatkova, L.; Dedic, T.; Seeman, T.; Lebl, J.; Pruhova, S. Hepatic phenotypes of HNF1B gene mutations: A case of neonatal cholestasis requiring portoenterostomy and literature review. World J. Gastroenterol. 2015, 21, 2550–2557.
  20. Kettunen, J.L.T.; Parviainen, H.; Miettinen, P.J.; Färkkilä, M.; Tamminen, M.; Salonen, P.; Lantto, E.; Tuomi, T. Biliary Anomalies in Patients with HNF1B Diabetes. J. Clin. Endocrinol. Metab. 2017, 102, 2075–2082.
  21. Hucthagowder, V.; Liu, T.C.; Paciorkowski, A.R.; Thio, L.L.; Keller, M.S.; Anderson, C.D.; Herman, T.; Dehner, L.P.; Grange, D.K.; Kulkarni, S. Chromosome 2p15p16.1 microdeletion syndrome: 2.5 Mb deletion in a patient with renal anomalies, intractable seizures and a choledochal cyst. Eur. J. Med. Genet. 2012, 55, 485–489.
  22. Hodgson, S.V.; Coonar, A.S.; Hanson, P.J.; Cottrell, S.; Scriven, P.N.; Jones, T.; Hawley, P.R.; Wilkinson, M.L. Two cases of 5q deletions in patients with familial adenomatous polyposis: Possible link with Caroli’s disease. J. Med. Genet. 1993, 30, 369–375.
  23. Parada, L.A.; Hallén, M.; Hägerstrand, I.; Tranberg, K.G.; Johansson, B. Clonal chromosomal abnormalities in congenital bile duct dilatation (Caroli’s disease). Gut 1999, 45, 780–782.
  24. Piccione, M.; Piro, E.; Serraino, F.; Cavani, S.; Ciccone, R.; Malacarne, M.; Pierluigi, M.; Vitaloni, M.; Zuffardi, O.; Corsello, G. Interstitial deletion of chromosome 2p15-16.1: Report of two patients and critical review of current genotype-phenotype correlation. Eur. J. Med. Genet. 2012, 55, 238–244.
  25. Lévy, J.; Coussement, A.; Dupont, C.; Guimiot, F.; Baumann, C.; Viot, G.; Passemard, S.; Capri, Y.; Drunat, S.; Verloes, A.; et al. Molecular and clinical delineation of 2p15p16.1 microdeletion syndrome. Am. J. Med. Genet. A 2017, 173, 2081–2087.
  26. Jorgez, C.J.; Rosenfeld, J.A.; Wilken, N.R.; Vangapandu, H.V.; Sahin, A.; Pham, D.; Carvalho, C.M.; Bandholz, A.; Miller, A.; Weaver, D.D.; et al. Genitourinary defects associated with genomic deletions in 2p15 encompassing OTX1. PLoS ONE 2014, 9, e107028.
  27. Florisson, J.M.; Mathijssen, I.M.; Dumee, B.; Hoogeboom, J.A.; Poddighe, P.J.; Oostra, B.A.; Frijns, J.P.; Koster, L.; de Klein, A.; Eussen, B.; et al. Complex craniosynostosis is associated with the 2p15p16.1 microdeletion syndrome. Am. J. Med. Genet. A 2013, 161, 244–253.
  28. de Leeuw, N.; Pfundt, R.; Koolen, D.A.; Neefs, I.; Scheltinga, I.; Mieloo, H.; Sistermans, E.A.; Nillesen, W.; Smeets, D.F.; de Vries, B.B.; et al. A newly recognised microdeletion syndrome involving 2p15p16.1: Narrowing down the critical region by adding another patient detected by genome wide tiling path array comparative genomic hybridisation analysis. J. Med. Genet. 2008, 45, 122–124.
  29. Bagheri, H.; Badduke, C.; Qiao, Y.; Colnaghi, R.; Abramowicz, I.; Alcantara, D.; Dunham, C.; Wen, J.; Wildin, R.S.; Nowaczyk, M.J.; et al. Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis. JCI Insight 2016, 1, e85461.
  30. Vieira, J.; Pinto, C.; Afonso, M.; do Bom Sucesso, M.; Lopes, P.; Pinheiro, M.; Veiga, I.; Henrique, R.; Teixeira, M.R. Identification of previously unrecognized FAP in children with Gardner fibroma. Eur. J. Hum. Genet. 2015, 23, 715–718.
  31. Li, J.; Woods, S.L.; Healey, S.; Beesley, J.; Chen, X.; Lee, J.S.; Sivakumaran, H.; Wayte, N.; Nones, K.; Waterfall, J.J.; et al. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant. Am. J. Hum. Genet. 2016, 98, 830–842.
  32. Meier, T.; Timm, M.; Montani, M.; Wilkens, L. Gene networks and transcriptional regulators associated with liver cancer development and progression. BMC Med. Genom. 2021, 14, 41.
  33. Cao, P.; Yang, A.; Li, P.; Xia, X.; Han, Y.; Zhou, G.; Wang, R.; Yang, F.; Li, Y.; Zhang, Y.; et al. Genomic gain of RRS1 promotes hepatocellular carcinoma through reducing the RPL11-MDM2-p53 signaling. Sci Adv. 2021, 7, 4304.
  34. Soares, K.C.; Goldstein, S.D.; Ghaseb, M.A.; Kamel, I.; Hackam, D.J.; Pawlik, T.M. Pediatric choledochal cysts: Diagnosis and current management. Pediatr. Surg. Int. 2017, 33, 637–650.
  35. Moslim, M.A.; Takahashi, H.; Seifarth, F.G.; Walsh, R.M.; Morris-Stiff, G. Choledochal Cyst Disease in a Western Center: A 30-Year Experience. J. Gastrointest. Surg. 2016, 20, 1453–1463.
  36. Madadi-Sanjani, O.; Wirth, T.C.; Kuebler, J.F.; Petersen, C.; Ure, B.M. Choledochal Cyst and Malignancy: A Plea for Lifelong Follow-Up. Eur. J. Pediatr. Surg. 2019, 29, 143–149.
  37. Lv, Y.; Xie, X.; Pu, L.; Wang, Q.; Pu, S.; Ai, C.; Liu, Y.; Chen, J.; Xiang, B. Molecular Characteristics of Choledochal Cysts in Children: Transcriptome Sequencing. Front. Genet. 2021, 12, 709340.
  38. Muthucumaru, M.; Ljuhar, D.; Panabokke, G.; Paul, E.; Nataraja, R.; Ferguson, P.; Dagia, C.; Clarnette, T.; King, S. Acute pancreatitis complicating choledochal cysts in children. J. Paediatr. Child. Health 2017, 53, 291–294.
  39. Fujishiro, J.; Masumoto, K.; Urita, Y.; Shinkai, T.; Gotoh, C. Pancreatic complications in pediatric choledochal cysts. J. Pediatr. Surg. 2013, 48, 1897–1902.
  40. Xue, Z.; Huang, K.; Cai, C.; Cai, L.; Jiang, C.Y.; Feng, Y.; Liu, Z.; Zeng, Q.; Cheng, L.; Sun, Y.E.; et al. Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing. Nature 2013, 500, 593–597.
  41. Wang, Y.; Li, X.; Ruiz, R. Weighted General Group Lasso for Gene Selection in Cancer Classification. IEEE Trans. Cybern 2019, 49, 2860–2873.
  42. Scavo, M.P.; Depalo, N.; Rizzi, F.; Ingrosso, C.; Fanizza, E.; Chieti, A.; Messa, C.; Denora, N.; Laquintana, V.; Striccoli, M.; et al. FZD10 Carried by Exosomes Sustains Cancer Cell Proliferation. Cells 2019, 8, 777.
  43. Noll, A.T.; Cramer, T.; Olde Damink, S.W.; Schaap, F.G. Cholangiocarcinoma, gone without the Wnt? World J. Hepatol. 2016, 8, 1093–1096.
  44. Rizvi, S.; Gores, G.J. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 2013, 145, 1215–1229.
  45. Montal, R.; Sia, D.; Montironi, C.; Leow, W.Q.; Esteban-Fabró, R.; Pinyol, R.; Torres-Martin, M.; Bassaganyas, L.; Moeini, A.; Peix, J.; et al. Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma. J. Hepatol. 2020, 73, 315–327.
  46. Jusakul, A.; Cutcutache, I.; Yong, C.H.; Lim, J.Q.; Huang, M.N.; Padmanabhan, N.; Nellore, V.; Kongpetch, S.; Ng, A.W.T.; Ng, L.M.; et al. Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma. Cancer Discov. 2017, 7, 1116–1135.
  47. Wong, J.K.; Campbell, D.; Ngo, N.D.; Yeung, F.; Cheng, G.; Tang, C.S.; Chung, P.H.; Tran, N.S.; So, M.T.; Cherny, S.S.; et al. Genetic study of congenital bile-duct dilatation identifies de novo and inherited variants in functionally related genes. BMC Med. Genom. 2016, 9, 75.
  48. Ziv, A.; Werner, L.; Konnikova, L.; Awad, A.; Jeske, T.; Hastreiter, M.; Mitsialis, V.; Stauber, T.; Wall, S.; Kotlarz, D.; et al. An RTEL1 Mutation Links to Infantile-Onset Ulcerative Colitis and Severe Immunodeficiency. J. Clin. Immunol. 2020, 40, 1010–1019.
  49. Wargo, J.J.; Carr, D.R.; Plaza, J.A.; Verschraegen, C.F. Metastatic Spiradenocarcinoma Managed with PD-1 Inhibition. J. Natl. Compr. Cancer Netw. 2022, 20, 1–3.
  50. Walne, A.J.; Vulliamy, T.; Kirwan, M.; Plagnol, V.; Dokal, I. Constitutional mutations in RTEL1 cause severe dyskeratosis congenita. Am. J. Hum. Genet. 2013, 92, 448–453.
  51. Vannier, J.B.; Sarek, G.; Boulton, S.J. RTEL1: Functions of a disease-associated helicase. Trends Cell Biol. 2014, 24, 416–425.
  52. Tompson, S.W.; Merriman, B.; Funari, V.A.; Fresquet, M.; Lachman, R.S.; Rimoin, D.L.; Nelson, S.F.; Briggs, M.D.; Cohn, D.H.; Krakow, D. A recessive skeletal dysplasia, SEMD aggrecan type, results from a missense mutation affecting the C-type lectin domain of aggrecan. Am. J. Hum. Genet. 2009, 84, 72–79.
  53. Hu, X.; Gui, B.; Su, J.; Li, H.; Li, N.; Yu, T.; Zhang, Q.; Xu, Y.; Li, G.; Chen, Y.; et al. Novel pathogenic ACAN variants in non-syndromic short stature patients. Clin. Chim. Acta 2017, 469, 126–129.
  54. Dubois, A.; Alonso-Sanchez, A.; Bajaj, V.; Husain, A.; Rajan, N. Multiple Facial Trichoepitheliomas and Vulval Cysts: Extending the Phenotypic Spectrum in CYLD Cutaneous Syndrome. JAMA Dermatol. 2017, 153, 826–828.
  55. Choi, A.; Lao, R.; Ling-Fung Tang, P.; Wan, E.; Mayer, W.; Bardakjian, T.; Shaw, G.M.; Kwok, P.Y.; Schneider, A.; Slavotinek, A. Novel mutations in PXDN cause microphthalmia and anterior segment dysgenesis. Eur. J. Hum. Genet. 2015, 23, 337–341.
  56. Cao, Y.; Guan, X.; Li, S.; Wu, N.; Chen, X.; Yang, T.; Yang, B.; Zhao, X. Identification of variants in ACAN and PAPSS2 leading to spondyloepi(meta)physeal dysplasias in four Chinese families. Mol. Genet. Genom. Med. 2022, 10, e1916.
  57. Meng, D.; Li, Z.; Ma, X.; Wu, L.; Fu, L.; Qin, G. ETV5 overexpression contributes to tumor growth and progression of thyroid cancer through PIK3CA. Life Sci. 2020, 253, 117693.
  58. Mei, Z.B.; Duan, C.Y.; Li, C.B.; Cui, L.; Ogino, S. Prognostic role of tumor PIK3CA mutation in colorectal cancer: A systematic review and meta-analysis. Ann. Oncol. 2016, 27, 1836–1848.
  59. Martínez-Sáez, O.; Chic, N.; Pascual, T.; Adamo, B.; Vidal, M.; González-Farré, B.; Sanfeliu, E.; Schettini, F.; Conte, B.; Brasó-Maristany, F.; et al. Frequency and spectrum of PIK3CA somatic mutations in breast cancer. Breast Cancer Res. 2020, 22, 45.
  60. Madsen, R.R.; Vanhaesebroeck, B.; Semple, R.K. Cancer-Associated PIK3CA Mutations in Overgrowth Disorders. Trends Mol. Med. 2018, 24, 856–870.
  61. Herberts, C.; Murtha, A.J.; Fu, S.; Wang, G.; Schönlau, E.; Xue, H.; Lin, D.; Gleave, A.; Yip, S.; Angeles, A.; et al. Activating AKT1 and PIK3CA Mutations in Metastatic Castration-Resistant Prostate Cancer. Eur. Urol. 2020, 78, 834–844.
  62. Quénet, D.; Gasser, V.; Fouillen, L.; Cammas, F.; Sanglier-Cianferani, S.; Losson, R.; Dantzer, F. The histone subcode: Poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 control cell differentiation by regulating the transcriptional intermediary factor TIF1beta and the heterochromatin protein HP1alpha. FASEB J. 2008, 22, 3853–3865.
  63. Park, H.H.; Kim, H.R.; Park, S.Y.; Hwang, S.M.; Hong, S.M.; Park, S.; Kang, H.C.; Morgan, M.J.; Cha, J.H.; Lee, D.; et al. RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment. Mol. Cancer 2021, 20, 107.
  64. Czerwińska, P.; Mazurek, S.; Wiznerowicz, M. The complexity of TRIM28 contribution to cancer. J. Biomed. Sci. 2017, 24, 63.
  65. Cammas, F.; Herzog, M.; Lerouge, T.; Chambon, P.; Losson, R. Association of the transcriptional corepressor TIF1beta with heterochromatin protein 1 (HP1): An essential role for progression through differentiation. Genes Dev. 2004, 18, 2147–2160.
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Update Date: 24 Jun 2022