Yıl: 2021 Cilt: 31 Sayı: 1 Sayfa Aralığı: 43 - 49 Metin Dili: İngilizce DOI: 10.4999/uhod.214010 İndeks Tarihi: 01-06-2023

V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution

Öz:
Genomic characterization of BRAF mutation in colorectal cancer (CRC) revolutionized it’s management. Current knowledge regard ing BRAF mutant CRC is based on the prevalent V600E mutation and mostly on Western population. However, CRC is known to be a complex and heterogenous disease. Thus, we aim to characterize the molecular, clinical and epidemiologic features of V600E as well as non-V600E BRAF mutated CRC in Turkish population. Demographic, histopathologic, molecular and clinical data of V600E and non-V600E BRAF mutant, metastatic and non-metastatic CRC cases were retrospectively collected from a tertiary Oncology hospital. Thirty cases of BRAF mutant colorectal carcinoma was identified. BRAF mutations were V600E (66.7%), V600A (10.0%), V600G (3.3%), V600K (3.3%), and L597V (16.7%). BRAF V600E cases had similar characteristics with Western population: frequent in females (45.0%), more proximal location (52.6%), aggressive histopathologic features (LVI 50.0%), and a worse prognosis (OS 13 vs 30 months, p= 0.068). Non-V600E BRAF mutant cases were diferred from V600E cases by being more frequent in males (50.0%), located more distally (60.0%), and carrying a better prognosis. This study demonstrates V600E mutation in CRC in Turkey is similar with Western population. In like manner, non-V600E BRAF mutation in CRC bears the potential to be a significant attribute for both prognostic and therapeutic implications as well.
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  • 1 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 66: 7-30, 2016.
  • 2 Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116: 855-867, 2004.
  • 3 Rowland A, Dias MM, Wiese MD, et al. Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti EGFR monoclonal antibody therapy for RAS wild-type meta static colorectal cancer. Br J Cancer 112: 1888-1894, 2015.
  • 4 Pietrantonio F, Petrelli F, Coinu A, et al. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer 51: 587-594, 2015.
  • 5 Nelson DS, Quispel W, Badalian-Very G, et al. Somatic acti vating ARAF mutations in Langerhans cell histiocytosis. Blood 123: 3152-3155, 2014.
  • 6 Siroy AE, Boland GM, Milton DR, et al. Beyond BRAFV600: Clinical Mutation Panel Testing by Next-Generation Sequenc ing in Advanced Melanoma. J Invest Dermatol 135: 508-515, 2015.
  • 7 Menzies AM, Haydu LE, Visintin L, et al. Distinguishing clin icopathologic features of patients with V600E and V600K <em>BRAF</em>-mutant metastatic melanoma. Clin Can cer Res 18: 3242-3249, 2012.
  • 8 Marchetti A, Felicioni L, Malatesta S, et al. Clinical features and outcome of patients with non–small-cell lung cancer har boring BRAF mutations. J Clin Oncol 29: 3574-3579, 2011.
  • 9 Jones JC, Renfro LA, Al-Shamsi HO, et al. Non-V600BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer. J Clin Oncol 35: 2624-2630, 2017.
  • 10 Shinozaki E, Yoshino T, Yamazaki K, et al. Clinical signifi cance of BRAF non-V600E mutations on the therapeutic ef fects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Compre hensive Cancer genomics (BREAC) study. Br J Cancer 117: 1450-1458, 2017.
  • 11 Guinney J, Dienstmann R, Wang X, et al.The consensus molecular subtypes of colorectal cancer. Nat Med 21: 1350- 1356, 2015.
  • 12 Van Cutsem E, Dekervel J. Not all BRAF-mutant metastatic colorectal cancers are identical: distinct clinical consequenc es of (non-V600) BRAF Mutations. J Clin Oncol 35: 2598- 2599, 2017.
  • 13 Sanz-Garcia E, Argiles G, Elez E, Tabernero J. BRAF mutant colorectal cancer: prognosis, treatment, and new perspec tives. Annal Oncol 28: 2648-2657, 2017.
  • 14 Loupakis F, Cremolini C, Salvatore L, et al. FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant meta static colorectal cancer. European journal of cancer (Oxford, England : 1990) 50: 57-63, 2014.
  • 15 Sanz-Garcia E, Argiles G, Elez E, Tabernero J. BRAF mutant colorectal cancer: prognosis, treatment, and new perspec tives. Ann Oncol 28: 2648-2657, 2017.
  • 16 Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin 65: 87-108, 2015.
  • 17 Favoriti P, Carbone G, Greco M, et al. Worldwide burden of colorectal cancer: a review. Upd Surg 68: 7-11, 2016.
  • 18 Phua LC, Ng HW, Yeo AH, et al. Prevalence of KRAS, BRAF, PI3K and EGFR mutations among Asian patients with meta static colorectal cancer. Oncol Lett 10: 2519-2526, 2015.
  • 19 Zhang J, Zheng J, Yang Y, et al. Molecular spectrum of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese colo rectal cancer patients: analysis of 1,110 cases. Sci Rep 5: 18678, 2015.
  • 20 Siraj AK, Prabhakaran S, Bavi P, et al. Prevalence of Lynch syndrome in a Middle Eastern population with colorectal can cer. Cancer 121: 1762-1771, 2015.
  • 21 Ozen F, Ozdemir S, Zemheri E, et al. The proto-oncogene KRAS and BRAF profiles and some clinical characteristics in colorectal cancer in the Turkish population. Genet Test Mol Biomarkers 17: 135-139, 2013.
  • 22 Gorukmez O, Yakut T, Gorukmez O, et al. Distribution of KRAS and BRAF mutations in metastatic colorectal cancers in Turkish Patients. Asian Pac J Cancer Prev 17: 1175-1179, 2016.
  • 23 Scartozzi M, Giampieri R, Aprile G, et al. The distinctive mo lecular, pathological and clinical characteristics of BRAF-mu tant colorectal tumors. Expert Rev Mol Diagn 15: 979-987, 2015.
  • 24 Vilkin A, Niv Y, Nagasaka T, et al. Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Is rael. Cancer 115: 760-769, 2009.
  • 25 Saridaki Z, Tzardi M, Sfakianaki M, et al. BRAFV600E mu tation analysis in patients with metastatic colorectal cancer (mCRC) in daily clinical practice: correlations with clinical characteristics, and its impact on patients’ outcome. PloS one 8: e84604, 2013.
  • 26 Beg S, Siraj AK, Prabhakaran S, et al. Molecular markers and pathway analysis of colorectal carcinoma in the Middle East. Cancer 121: 3799-3808, 2015.
  • 27 Masoomi H, Ziogas A, Lin BS, et al. Population-based evalu ation of adenosquamous carcinoma of the colon and rectum. Dis Colon Rectum 55: 509-514, 2012.
  • 28 Cremolini C, Di Bartolomeo M, Amatu A, et al. BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann On col 26: 2092-2097, 2015.
APA Simsek C, esin e, Lacin S, yalcin s (2021). V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. , 43 - 49. 10.4999/uhod.214010
Chicago Simsek Cem,esin ece,Lacin Sahin,yalcin suayib V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. (2021): 43 - 49. 10.4999/uhod.214010
MLA Simsek Cem,esin ece,Lacin Sahin,yalcin suayib V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. , 2021, ss.43 - 49. 10.4999/uhod.214010
AMA Simsek C,esin e,Lacin S,yalcin s V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. . 2021; 43 - 49. 10.4999/uhod.214010
Vancouver Simsek C,esin e,Lacin S,yalcin s V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. . 2021; 43 - 49. 10.4999/uhod.214010
IEEE Simsek C,esin e,Lacin S,yalcin s "V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution." , ss.43 - 49, 2021. 10.4999/uhod.214010
ISNAD Simsek, Cem vd. "V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution". (2021), 43-49. https://doi.org/10.4999/uhod.214010
APA Simsek C, esin e, Lacin S, yalcin s (2021). V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. Uluslararası Hematoloji-Onkoloji Dergisi, 31(1), 43 - 49. 10.4999/uhod.214010
Chicago Simsek Cem,esin ece,Lacin Sahin,yalcin suayib V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. Uluslararası Hematoloji-Onkoloji Dergisi 31, no.1 (2021): 43 - 49. 10.4999/uhod.214010
MLA Simsek Cem,esin ece,Lacin Sahin,yalcin suayib V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. Uluslararası Hematoloji-Onkoloji Dergisi, vol.31, no.1, 2021, ss.43 - 49. 10.4999/uhod.214010
AMA Simsek C,esin e,Lacin S,yalcin s V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. Uluslararası Hematoloji-Onkoloji Dergisi. 2021; 31(1): 43 - 49. 10.4999/uhod.214010
Vancouver Simsek C,esin e,Lacin S,yalcin s V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution. Uluslararası Hematoloji-Onkoloji Dergisi. 2021; 31(1): 43 - 49. 10.4999/uhod.214010
IEEE Simsek C,esin e,Lacin S,yalcin s "V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution." Uluslararası Hematoloji-Onkoloji Dergisi, 31, ss.43 - 49, 2021. 10.4999/uhod.214010
ISNAD Simsek, Cem vd. "V600E and Non-V600E BRAF Mutations in Colorectal Cancer: Clinicopathologic Correlations in a Single Institution". Uluslararası Hematoloji-Onkoloji Dergisi 31/1 (2021), 43-49. https://doi.org/10.4999/uhod.214010