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Kirsten Rat Sarcoma Viral Oncogene Homolog Mutations: Comparison
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Please note this is a comparison between Version 2 by Camila Xu and Version 1 by Samantha Epistolio.

The Rat Sarcoma virus (RAS) gene family is characterized by three genes (KRAS, NRAS and HRAS) encoding for closely related GTPase proteins responsible for the signal transduction within the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways. KRAS mutations are the most important and frequent alterations in this family, accounting for 85% of RAS mutations observed in the oncologic population.

  • KRAS
  • lung adenocarcinoma
  • KRAS biology
  • prognosis

1. Introduction

The Rat Sarcoma virus (RAS) gene family is characterized by three genes (KRAS, NRAS and HRAS) encoding for closely related GTPase proteins responsible for the signal transduction within the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways. This group of genes is associated with the control of cell growth, survival and differentiation [1[1][2],2], and it is characterized by the most frequently observed genomic alterations in human cancers, being detected in approximately 19% of tumors [3,4][3][4].
KRAS mutations are the most important and frequent alterations in this family, accounting for 85% of RAS mutations observed in the oncologic population [5]. More specifically, KRAS exon 2, exon 3 and exon 4 mutations are present in 13.98%, 1.17% and 0.62% of all cancer types [2[2][6],6], respectively, especially in pancreatic ductal adenocarcinoma (PDAC) (88% of patients), in colorectal cancer (CRC) (45–50% of cases) and in lung adenocarcinoma (AC) (30–35% of patients) (Table 1) [5,6,7,8][5][6][7][8].
Table 1.
 Cancers with the highest 
KRAS
 mutations frequencies.
Cancer KRAS Mutations Percentage
PDAC 88%
CRC 45–50%
Lung AC 30–35%
AC: AdenoCarcinoma; CRC: ColoRectal Cancer; PDAC: Pancreatic Ductal AdenoCarcinoma (AACR Project GENIE Consortium, 2017 [7]; Prior et al., 2020 [6]; Uras et al., 2020 [8]; Reck et al., 2021 [5]).

2. KRAS Mutations in Lung Cancer

The protein encoded by KRAS is a GTPase regulated by tyrosine kinase receptors that in turn activate the RAF/MEK/MAPK and PI3K/AKT signaling pathways, leading to a strong promotion of cell growth and replication that determines cell survival. The presence of mutations in KRAS blocks this protein in the active GTP-bound conformation, thereby activating constitutively downstream signaling pathways, finally resulting in uncontrolled cell growth [11][9]. Specifically, this continuous activation confers to cancer cells the ability to grow in lower glucose concentrations than those required for the growth of normal cells or cancer cells that do not have KRAS mutations [12,13][10][11]. As for other cancer types, KRAS mutations in lung cancers typically occur in hot-spot codons of exons 2, 3 and 4.

2.1. KRAS Mutations in NSCLC

In general, lung cancer has a complex and heterogeneous background. Indeed, it can be histologically subdivided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), accounting for 85% and 15% of all lung neoplasia, respectively [14][12]. NSCLCs are further subdivided into three histologic types: AC, squamous-cell carcinoma (SCC) and large-cell carcinoma (LCC), which represent 40%, 25–30% and 5–10% of all lung cancers, respectively [8]. The occurrence of KRAS mutations differs based on the specific lung cancer type/subtype, being higher in NSCLC than in SCLC, and within NSCLC, KRAS mutations are more frequent in lung AC than SCC (Table 2). Interestingly, a recent study established two different groups of KRAS-mutant NSCLC, KRAS-dependent and KRAS-independent according to their requirement for KRAS mutations to maintain oncogenicity. However, to date, these data are preliminary and need to be confirmed in larger cohorts [11][9].
Table 2.
 Rates of 
KRAS
 mutations in NSCLC and subtypes.
Cancer Mutation Rates
KRAS KRAS Exon 2 Mutations Rate KRAS Exon 3 Mutations Rate KRAS Exon 4 Rate Considering the Total of KRAS Mutations
NSCLC 25–30% 34% 1.89% 0.24%
Lung AC 30–35% 27% 7% <1%
SCC 3–4% 7% <3% <0.5%
AC: AdenoCarcinoma; NSCLC: Non-Small Cell Lung Cancer; SCC: Squamous-Cell Carcinoma (AACR Project GENIE Consortium, 2017 [7]).

2.1.1. KRAS Mutations in Lung Adenocarcinoma

In the AC subtype, almost 30–35% of cases are driven by a KRAS mutation [5[5][6][7][8],6,7,8], mainly in exon 2, with the c.34G > T (p.G12C) change being the most prevalent (Table 3) [15][13].
Table 3.
 Rates of 
KRAS
 exons 2, 3 and 4 mutations in NSCLC.
KRAS Mutations Frequencies
Exon 2 codon 12  
c.34G > T (p.G12C) 40%
c.35G > T (p.G12V) 19–21%
c.35G > A (p.G12D) 15–17%
c.35G > C (p.G12A) 6%
c.34G > A (p.G12S) 4%
c.34G > C (p.G12R) 4%
Exon 2 codon 13  
c.37G > T (p.G13C) 6.8%
c.38G > A (p.G13D) 0.8%
c.37G > C (p.G13R) 0.6%
c.37G > A (p.G13S) NR
Exon 3 codon 59  
c.176C > A (p.A59E) NR
c.176C > G (p.A59G) NR
c.175G > A (p.A59T) NR
Exon 3 codon 61 NR
c.183A > C (p.Q61H) 1.2%
c.182A > T (p.Q61L) 0.4%
c.182A > G (p.Q61R) 0.06%
c.180_181delinsAA (p.Q61K) 0.02%
c.181C > G (p.Q61E) NR
Exon 4 codon 146  
c.436G > C (p.A146P) NR
c.436G > A (p.A146T) NR
c.437C > T (p.A146V) NR
NR: Not Relevant; NSCLC: Non-Small Cell Lung Cancer (AACR Project GENIE Consortium, 2017 [7]).

3. KRAS Mutations in Population-Based Cohorts of Lung Adenocarcinomas

The frequency of KRAS mutation in patients affected by lung AC differs among ethnicities and countries of origin, being higher in Caucasian (where they are detected in up to 30% of patients) than in Asians or in Africans (occurring in 16% and 9% of cases, respectively) [19,20,21,22,23,24,25][14][15][16][17][18][19][20].

3.1. KRAS Mutations in Caucasians Affected by Lung AC

In Europe, the most frequent KRAS mutations in lung AC are found in exon 2, with a general mutational rate close to 30% [19,20,21][14][15][16]. Differences can also be observed among European countries (28% in Germany, 29–31% in France, 27% in Italy, 19–27% in Greece and 43.3% in Spain) [19,20,21,26,27,28,29][14][15][16][21][22][23][24] and even among regions of the same country: for example, the island of Sardinia in Italy has the lowest frequency among all Italian regions [30][25]. This difference could be due to the physical separation of the island from the country, reflecting different lifestyle or environmental behaviors. In Europe, 86% of mutations in exon 2 are located in codon 12, with the c.34G > T (p.G12C) mutation being the most common one (observed in 34% of cases) [19][14] (Table 4).
Table 4.
 Rates of 
KRAS
 mutations in lung AC subdivided in different ethnicities.
KRAS Mutation Rates
Caucasians Asians Africans Americans
KRAS exon2        
c.34G > T (p.G12C) 34% 24.5% NA 41.2%
c.35G > T (p.G12V) 21% 1.5% NA 19%
c.35G > A (p.G12D) 14% 25.5% 28.5% 15%
c.35G > C (p.G12A) 9.5% 1.3% NA 7%
c.34G > A (p.G12S) 1% 0.6% NA 1%
c.34G > C (p.G12R) 1% 0.6% NA 1%
c.37G > T (p.G13C) 4% 0.7% NA 7%
c.38G > A (p.G13D) 1–2% 0.7% 42.8% 1%
c.37G > C (p.G13R) 0.5% 0.5% NA 0.5%
c.37G > A (p.G13S) NR NR NR NR
KRAS exon3        
c.183A > C (p.Q61H) 1% 0.8% NA 4%
c.182A > T (p.Q61L) 0.5% 0.4% NA 1%
c.182A > G (p.Q61R) 0.06% 0.05% NA 0.05
c.180_181delinsAA (p.Q61K) 0.02% NR NA 0.02
c.181C > G (p.Q61E) NR NR NA NR
c.176C > A (p.A59E) NR NR NA NR
c.176C > G (p.A59G) NR NR NA NR
c.175G > A (p.A59T) NR NR NA NR
KRAS exon4 NR NR NA NR
c.436G > C (p.A146P) NR NR NA NR
c.436G > A (p.A146T) NR NR NA NR
c.437C > T (p.A146V) NR NR NA NR
AC, AdenoCarcinoma; NA: Not Available; NR: Not Relevant (Boch et al., 2013 [19][14]; Elghissassi et al., 2014 [31][26]; Kim et al., 2014 [32][27]; Li et al., 2014 [33][28]; Nadal et al., 2014 [34][29]; Arrieta and Ramírez-Tirado et al., 2015 [35][30]; Dhieb et al., 2019 [36][31]; Judd et al., 2021 [18][32]).

3.2. KRAS Mutations in Asians Affected by Lung AC

Several studies show that Asian populations have significant lower KRAS mutation incidence than that in the Caucasian and Afro-American populations [37,38][33][34]. As for Europe, even in Asia there is a wide range in the mutation frequencies among countries, with the highest values in Vietnam (21%, close to European populations) and the lowest in China (8.4–13%), Japan (10%) and Indonesia (7%) [33,39,40,41,42][28][35][36][37][38]. As usual, the most affected region is KRAS exon 2, but the most common KRAS exon 2 mutational subtype is the c.35G > A (p.G12D) change, with a rate of 25.5%, followed by c.34G > T (p.G12C) (24.5%) [22,32,43][17][27][39] (Table 4). The frequency and type of mutations in exons 3 and 4 in Asian populations mirror those observed in European countries [43][39] (Table 4).

3.3. KRAS Mutations in Africans Affected by Lung AC

Central and West Africa are the regions with the lowest incidence rates of lung cancer for both sexes (0.8%) worldwide [44][40], while in North Africa, the KRAS mutations is observed in 6–9% of patients [31,36,45][26][31][41]. Specific studies concerning molecular characterization in African populations are extremely rare, and the data are sporadic. In Morocco, the c.34G > T (p.G12C) change is the most prevalent one (detected in 73% of KRAS-mutant cases) [31][26], while in Tunisia, c.38G > A (p.G13D) followed by c.35G > A (p.G12D) are predominant (42.8% and 28.5% of cases, respectively) [36][31] (Table 4). However, the size cohort is often too small to derive any conclusion.

3.4. KRAS Mutations in the Heterogeneous Lung AC American Population

In the USA, KRAS mutations are observed in a significantly high proportion of cases, up to 47.5% of patients, especially in exon 2 (90.6%), with the c.34G > T (p.G12C) change being the most prevalent one (41.2%) [34][29]. Focusing on the different ethnicities, the prevalence of KRAS mutations in African-American patients was less than that observed in the Caucasian group (17% versus 26%) [46][42]. Interestingly, American Hispanic patients have better survival than non-Hispanic/non-African cases, despite the fact that this population is diagnosed for cancer at a later stage due to social factors. This situation, defined also as the “Hispanic paradox”, has suggested investigating Hispanic individuals’ biological, pathological and molecular factors [35][30]. First, researchers observed a lower frequency of KRAS mutations compared with the Caucasian population (15.7% and 20–35% respectively) [35][30], and, second, researchers described that Hispanics have more KRAS changes in exon 2 codon 13 and in exon 3 codon 59 than non-Hispanics [47][43], possibly explaining the inferior cancer aggressiveness. In Latin America, the frequency of NSCLC (in particular lung AC) with KRAS mutations corresponds to 14% [48][44], with little differences, ranging from 12.9% in Colombia to 15.9% in Mexico and 16.8% in Peru [48][44]. Two relevant observations come from analyses of Puerto Rican and Brazilian cohorts [49,50][45][46]. In Puerto Rico, lung ACs present with KRAS mutations in 18.7% of the cases, a rate that is significantly higher than in the aforementioned general Hispanic populations [48,50][44][46]; in Brazil, 14.6% of lung ACs harbour KRAS mutations, with a higher prevalence in non-Asian patients [49][45]: in both populations, c.34G > T (p.G12C) is the most diffused type of alteration.

References

  1. Malumbres, M.; Barbacid, M. RAS oncogenes: The first 30 years. Nat. Cancer 2003, 3, 459–465, Erratum in: Nat. Rev. Cancer 2003, 3, 708.
  2. Chen, K.; Zhang, Y.; Qian, L.; Wang, P. Emerging strategies to target RAS signaling in human cancer therapy. J. Hematol. Oncol. 2021, 14, 116.
  3. Moore, A.R.; Rosenberg, S.C.; McCormick, F.; Malek, S. RAS-targeted therapies: Is the undruggable drugged? Nat. Rev. Drug Discov. 2020, 19, 533–552, Erratum in: Nat. Rev. Drug. Discov. 2020, 19, 902.
  4. Wang, C.; Fakih, M. Targeting KRAS in Colorectal Cancer. Curr. Oncol. Rep. 2021, 23, 28.
  5. Reck, M.; Carbone, D.; Garassino, M.; Barlesi, F. Targeting KRAS in non-small-cell lung cancer: Recent progress and new approaches. Ann. Oncol. 2021, 32, 1101–1110.
  6. Prior, I.A.; Hood, F.E.; Hartley, J.L. The Frequency of Ras Mutations in Cancer. Cancer Res. 2020, 80, 2969–2974.
  7. The AACR Project GENIE Consortium; André, F.; Arnedos, M.; Baras, A.S.; Baselga, J.; Bedard, P.L.; Berger, M.F.; Bierkens, M.; Calvo, F.; Cerami, E.; et al. AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov. 2017, 7, 818–831.
  8. Uras, I.Z.; Moll, H.P.; Casanova, E. Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future. Int. J. Mol. Sci. 2020, 21, 4325.
  9. Román, M.; Baraibar, I.; López, I.; Nadal, E.; Rolfo, C.; Vicent, S.; Gil-Bazo, I. KRAS oncogene in non-small cell lung cancer: Clinical perspectives on the treatment of an old target. Mol. Cancer 2018, 17, 33.
  10. Yun, J.; Rago, C.; Cheong, I.; Pagliarini, R.; Angenendt, P.; Rajagopalan, H.; Schmidt, K.; Willson, J.K.V.; Markowitz, S.; Zhou, S.; et al. Glucose Deprivation Contributes to the Development of KRAS Pathway Mutations in Tumor Cells. Science 2009, 325, 1555–1559.
  11. Ying, H.; Kimmelman, A.C.; Lyssiotis, C.A.; Hua, S.; Chu, G.C.; Fletcher-Sananikone, E.; Locasale, J.W.; Son, J.; Zhang, H.; Coloff, J.L.; et al. Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism. Cell 2012, 149, 656–670.
  12. Nicholson, A.G.; Tsao, M.S.; Beasley, M.B.; Borczuk, A.C.; Brambilla, E.; Cooper, W.A.; Dacic, S.; Jain, D.; Kerr, K.M.; Lantuejoul, S.; et al. The 2021 WHO Classification of Lung Tumors: Impact of Advances since 2015. J. Thorac. Oncol. 2022, 17, 362–387.
  13. Edkins, S.; O’Meara, S. Recurrent KRAS codon 146 mutations in human colorectal cancer. Cancer Biol. Ther. 2006, 5, 928–932.
  14. Boch, C.; Kollmeier, J.; Roth, A.; Stephan-Falkenau, S.; Misch, D.; Grüning, W.; Bauer, T.T.; Mairinger, T. The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): Routine screening data for central Europe from a cohort study. BMJ Open 2013, 3, e002560.
  15. Renaud, S.; Falcoz, P.-E.; Schaëffer, M.; Guenot, D.; Romain, B.; Olland, A.; Reeb, J.; Santelmo, N.; Chenard, M.-P.; Legrain, M.; et al. Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases. Br. J. Cancer 2015, 113, 1206–1215.
  16. Sebastian, M.; Eberhardt, W.E.; Hoffknecht, P.; Metzenmacher, M.; Wehler, T.; Kokowski, K.; Alt, J.; Schütte, W.; Büttner, R.; Heukamp, L.C.; et al. KRAS G12C-mutated advanced non-small cell lung cancer: A real-world cohort from the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315). Lung Cancer 2021, 154, 51–61.
  17. Zhou, W.; Christiani, D.C. East meets West: Ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and Caucasians. Chin. J. Cancer 2011, 30, 287–292.
  18. Dearden, S.; Stevens, J.; Wu, Y.L.; Blowers, D. Mutation incidence and coincidence in non small-cell lung cancer: Meta-analyses by ethnicity and histology (mutMap). Ann. Oncol. 2019, 24, 2371–2376.
  19. Tímár, J. The clinical relevance of KRAS gene mutation in non-small-cell lung cancer. Curr. Opin. Oncol. 2014, 26, 138–144.
  20. Yang, H.; Liang, S.-Q.; Schmid, R.A.; Peng, R.-W. New Horizons in KRAS-Mutant Lung Cancer: Dawn after Darkness. Front. Oncol. 2019, 9, 953.
  21. Chatziandreou, I.; Tsioli, P.; Sakellariou, S.; Mourkioti, I.; Giannopoulou, I.; Levidou, G.; Korkolopoulou, P.; Patsouris, E.; Saetta, A.A. Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations. PLoS ONE 2015, 10, e0133859.
  22. Barlesi, F.; Mazieres, J.; Merlio, J.-P.; Debieuvre, D.; Mosser, J.; Lena, H.; Ouafik, L.H.; Besse, B.; Rouquette, I.; Westeel, V.; et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: Results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 2016, 387, 1415–1426.
  23. Gobbini, E.; Galetta, D.; Tiseo, M.; Graziano, P.; Rossi, A.; Bria, E.; Di Maio, M.; Rossi, G.; Gregorc, V.; Riccardi, F.; et al. Molecular profiling in Italian patients with advanced non-small-cell lung cancer: An observational prospective study. Lung Cancer 2017, 111, 30–37.
  24. Martorell, P.M.; Huerta, M.; Quilis, A.C.; Abellán, R.; Seda, E.; Blesa, S.; Chaves, F.J.; Beltrán, D.D.; Keränen, S.R.; Franco, J.; et al. Coexistence of EGFR, KRAS, BRAF, and PIK3CA Mutations and ALK Rearrangement in a Comprehensive Cohort of 326 Consecutive Spanish Nonsquamous NSCLC Patients. Clin. Lung Cancer 2017, 18, e395–e402.
  25. Colombino, M.; Sardinian Lung Cancer (SLC) Study Group; Paliogiannis, P.; Cossu, A.; Santeufemia, D.A.; Sini, M.C.; Casula, M.; Palomba, G.; Manca, A.; Pisano, M.; et al. EGFR, KRAS, BRAF, ALK, and cMET genetic alterations in 1440 Sardinian patients with lung adenocarcinoma. BMC Pulm. Med. 2019, 19, 209.
  26. Elghissassi, I.; Inrhaoun, H.; Boukir, A.; Kettani, F.; Gamra, L.; Mestari, A.; Jabri, L.; Bensouda, Y.; Mrabti, H.; Errihani, H. Frequency and Spectrum of KRAS Mutations in Moroccan Patients with Lung Adenocarcinoma. ISRN Oncol. 2014, 2014, 192493.
  27. Kim, E.Y.; Kim, A.; Kim, S.K.; Kim, H.J.; Chang, J.; Ahn, C.M.; Lee, J.S.; Shim, H.S.; Chang, Y.S. KRAS oncogene substitutions in Korean NSCLC patients: Clinical implication and relationship with pAKT and RalGTPases expression. Lung Cancer 2014, 85, 299–305.
  28. Li, S.; Li, L.; Zhu, Y.; Huang, C.; Qin, Y.; Liu, H.; Ren-heidenreich, L.; Shi, B.; Ren, H.; Chu, X.; et al. Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: A comprehensive mutation profiling from 5125 Chinese cohorts. Br. J. Cancer 2014, 110, 2812–2820.
  29. Nadal, E.; Chen, G.; Prensner, J.R.; Shiratsuchi, H.; Sam, C.; Zhao, L.; Kalemkerian, G.P.; Brenner, D.; Lin, J.; Reddy, R.M.; et al. KRAS-G12C Mutation Is Associated with Poor Outcome in Surgically Resected Lung Adenocarcinoma. J. Thorac. Oncol. 2014, 9, 1513–1522.
  30. Arrieta, O.; Ramírez-Tirado, L.-A.; Báez-Saldaña, R.; Peña-Curiel, O.; Soca-Chafre, G.; Macedo-Perez, E.-O. Different mutation profiles and clinical characteristics among Hispanic patients with non-small cell lung cancer could explain the “Hispanic paradox”. Lung Cancer 2015, 90, 161–166.
  31. Dhieb, D.; Belguith, I.; Capelli, L.; Chiadini, E.; Canale, M.; Bravaccini, S.; Yangui, I.; Boudawara, O.; Jlidi, R.; Boudawara, T.; et al. Analysis of Genetic Alterations in Tunisian Patients with Lung Adenocarcinoma. Cells 2019, 8, 514.
  32. Judd, J.; Karim, N.A.; Khan, H.; Naqash, A.R.; Baca, Y.; Xiu, J.; VanderWalde, A.M.; Mamdani, H.; Raez, L.E.; Nagasaka, M.; et al. Characterization of KRAS Mutation Subtypes in Non–small Cell Lung Cancer. Mol. Cancer Ther. 2021, 20, 2577–2584.
  33. Izumi, M.; Suzumura, T.; Ogawa, K.; Matsumoto, Y.; Sawa, K.; Yoshimoto, N.; Tani, Y.; Watanabe, T.; Kaneda, H.; Mitsuoka, S.; et al. Differences in molecular epidemiology of lung cancer among ethnicities (Asian vs. Caucasian). J. Thorac. Dis. 2020, 12, 3776–3784.
  34. Masykura, N.; Zaini, J.; Syahruddin, E.; Andarini, S.L.; Hudoyo, A.; Yasril, R.; Ridwanuloh, A.; Hidajat, H.; Nurwidya, F.; Utomo, A. Impact of smoking on frequency and spectrum of K-RAS and EGFR mutations in treatment naive Indonesian lung cancer patients. Lung Cancer Targets Ther. 2019, 10, 57–66.
  35. Matsumoto, S.; Tsuchihara, K.; Yoh, K.; Zenke, Y.; Kohno, T.; Ishii, G.; Tsuta, K.; Umemura, S.; Niho, S.; Ohmatsu, H.; et al. A new nationwide genomic screening system in Japan for the development of targeted therapies against advanced non-small lung cancers with rare driver mutations. J. Clin. Oncol. 2014, 32, 11007.
  36. Mehta, A.; Dobersch, S.; Romero-Olmedo, A.J.; Barreto, G. Epigenetics in lung cancer diagnosis and therapy. Cancer Metastasis Rev. 2015, 34, 229–241.
  37. Perri, F.; Pisconti, S.; Scarpati, G.D.V. P53 mutations and cancer: A tight linkage. Ann. Transl. Med. 2016, 4, 522.
  38. Dang, A.-T.H.; Tran, V.-U.; Tran, T.-T.; Pham, H.-A.T.; Le, D.-T.; Nguyen, L.; Nguyen, N.-V.; Nguyen, T.-H.T.; Nguyen, C.; Le, H.T.; et al. Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population. Sci. Rep. 2020, 10, 2707.
  39. Lee, J.; Tan, A.C.; Zhou, S.; Yoon, S.; Liu, S.; Masuda, K.; Hayashi, H.; Batra, U.; Kim, D.-W.; Goto, Y.; et al. Clinical Characteristics and Outcomes in Advanced KRAS-Mutated NSCLC: A Multicenter Collaboration in Asia (ATORG-005). JTO Clin. Res. Rep. 2021, 3, 100261.
  40. McIntyre, A.; Ganti, A.K. Lung cancer-A global perspective. J. Surg. Oncol. 2017, 115, 550–554.
  41. Mezni, F.; Mlika, M.; Boussen, H.; Ghedira, H.; Fenniche, S.; Faten, T.; Loriot, M.-A. About molecular profile of lung cancer in Tunisian patients. J. Immunoass. Immunochem. 2018, 39, 99–107.
  42. Reinersman, J.M.; Johnson, M.L.; Riely, G.J.; Chitale, D.A.; Nicastri, A.D.; Soff, G.A.; Schwartz, A.G.; Sima, C.S.; Ayalew, G.; Lau, C.; et al. Frequency of EGFR and KRAS Mutations in Lung Adenocarcinomas in African Americans. J. Thorac. Oncol. 2011, 6, 28–31.
  43. McQuitty, E.; Zhang, W.; Hendrickson, H.; Tio, F.O.; Jagirdar, J.; Olsen, R.; Cagle, P.T. Lung Adenocarcinoma Biomarker Incidence in Hispanic Versus Non-Hispanic White Patients. Arch. Pathol. Lab. Med. 2014, 138, 390–394.
  44. Arrieta, O.; Cardona, A.F.; Martín, C.; Más-López, L.; Corrales-Rodríguez, L.; Bramuglia, G.; Castillo-Fernandez, O.; Meyerson, M.; Amieva-Rivera, E.; Campos-Parra, A.D.; et al. Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). J. Thorac. Oncol. 2015, 10, 838–843.
  45. Bacchi, C.E.; Ciol, H.; Queiroga, E.M.; Benine, L.C.; Silva, L.H.; Ojopi, E.B. Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients. Clinics 2012, 67, 419–424.
  46. Zheng, R.; Yin, Z.; Alhatem, A.; Lyle, D.; You, B.; Jiang, A.S.; Liu, D.; Jobbagy, Z.; Wang, Q.; Aisner, S.; et al. Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico. Cancers 2020, 12, 3492.
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