Effectors of epidermal growth factor receptor pathway: the genetic profiling ofKRAS, BRAF, PIK3CA, NRAS mutations in colorectal cancer characteristics and personalized medicine

PloS One
Yinchen ShenYuankai Shi

Abstract

Mutations in KRAS oncogene are recognized biomarkers that predict lack of response to anti- epidermal growth factor receptor (EGFR) antibody therapies. However, some patients with KRAS wild-type tumors still do not respond, so other downstream mutations in BRAF, PIK3CA and NRAS should be investigated. Herein we used direct sequencing to analyze mutation status for 676 patients in KRAS (codons 12, 13 and 61), BRAF (exon 11 and exon 15), PIK3CA (exon 9 and exon 20) and NRAS (codons12, 13 and 61). Clinicopathological characteristics associations were analyzed together with overall survival (OS) of metastatic colorectal cancer patients (mCRC). We found 35.9% (242/674) tumors harbored a KRAS mutation, 6.96% (47/675) harbored a BRAF mutation, 9.9% (62/625) harbored a PIK3CA mutation and 4.19% (26/621) harbored a NRAS mutation. KRAS mutation coexisted with BRAF, PIK3CA and NRAS mutation, PIK3CA exon9 mutation appeared more frequently in KRAS mutant tumors (P = 0.027) while NRAS mutation almost existed in KRAS wild-types (P<0.001). Female patients and older group harbored a higher KRAS mutation (P = 0.018 and P = 0.031, respectively); BRAF (V600E) mutation showed a higher frequency in colon cancer and poor differentiation tumors (P = 0...Continue Reading

References

Jun 1, 1997·Japanese Journal of Clinical Oncology·W S WangP M Chen
Jan 2, 2003·Nature Reviews. Cancer·Julian Downward
Jun 5, 2003·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Jul 23, 2004·The New England Journal of Medicine·David CunninghamEric Van Cutsem
Jul 5, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Sérgia VelhoRaquel Seruca
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Li Zhao, Peter K Vogt
Mar 5, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rafael G AmadoDavid D Chang
Mar 14, 2008·The New England Journal of Medicine·Fortunato Ciardiello, Giampaolo Tortora
Jun 26, 2008·British Journal of Cancer·F CappuzzoP A Jänne
Sep 2, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Salvatore ArtaleSalvatore Siena
Oct 7, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F CappuzzoM Varella-Garcia
Oct 24, 2008·The New England Journal of Medicine·Christos S KarapetisJohn R Zalcberg
Nov 13, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federica Di NicolantonioAlberto Bardelli
Dec 31, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Carsten BokemeyerPiotr Koralewski
Feb 5, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Krishan KumarHassan Ashktorab
Feb 21, 2009·The New England Journal of Medicine·Antonio Marchetti, Giampietro Gasparini
Feb 25, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Shuji OginoCharles S Fuchs
Apr 25, 2009·The Cancer Journal·Antonio JimenoS Gail Eckhardt
Jul 29, 2009·Nature Reviews. Clinical Oncology·Nicola NormannoFortunato Ciardiello
Aug 15, 2009·Pathology, Research and Practice·Jens NeumannAndreas Jung
Sep 10, 2009·Journal of the National Cancer Institute·Salvatore SienaAlberto Bardelli
Nov 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Pierre Laurent-PuigFrédérique Penault-Llorca
Dec 17, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Arnaud D RothFred Bosman
Dec 19, 2009·The New England Journal of Medicine·Sanford D Markowitz, Monica M Bertagnolli
Jan 27, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alberto Bardelli, Salvatore Siena
Jul 24, 2010·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Wangjun LiaoRongcheng Luo
Aug 26, 2010·Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B·Natsumi IraharaShuji Ogino
Oct 28, 2010·JAMA : the Journal of the American Medical Association·Wendy De RoockSabine Tejpar
Mar 11, 2011·World Journal of Gastroenterology : WJG·Hong ShenShu Zheng
May 15, 2012·Clinica Chimica Acta; International Journal of Clinical Chemistry·Li-Ling HsiehTa-Chih Liu
Jun 27, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sabine TejparEric Van Cutsem
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Jan 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marc PeetersScott D Patterson
Jan 22, 2013·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal

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Citations

Jun 12, 2014·Cancer Chemotherapy and Pharmacology·Lei ChengXiao-Ping Qian
Dec 6, 2014·Hematology/oncology Clinics of North America·Sebastian StintzingHeinz-Josef Lenz
Jul 18, 2014·BioMed Research International·Tze-Kiong ErMarta Herreros-Villanueva
Feb 23, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Mayank JauhriShyam Aggarwal
May 1, 2018·Expert Review of Molecular Diagnostics·Eleonora LaiMario Scartozzi
Nov 6, 2018·Journal of the National Cancer Institute·Efrat L AmitayMichael Hoffmeister
Feb 11, 2015·World Journal of Gastroenterology : WJG·Ju-Xiang YeXue-Ying Shi
May 8, 2019·Indian Journal of Cancer·Ozturk Ates, Suayib Yalcin
Mar 21, 2017·Journal of Clinical Pathology·Sebastian LunkeMichael Christie
Sep 5, 2019·European Journal of Cancer Care·Mahmood MoosazadehFereshteh Rostami-Maskopaee
Jun 14, 2020·International Journal of Molecular Sciences·Enzo SpisniMaria Chiara Valerii
Jun 16, 2015·World Journal of Gastroenterology : WJG·Hong ShenYing Yuan
Dec 2, 2015·Oncology Letters·Rafał StecCezary Szczylik
Nov 30, 2018·International Journal of Molecular Sciences·Teodora CosteaMaria-Magdalena Mocanu
Jan 13, 2018·Cancer Metastasis Reviews·Dongdong HuangHonghe Zhang
Apr 24, 2018·Middle East Journal of Digestive Diseases·Hooria MomenzadehBita Geramizadeh
Nov 1, 2020·Scientific Reports·Alireza TabibzadehMohammad Hadi Karbalaie Niya
May 23, 2015·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Amanda I PhippsTerrilea Burnett
Jul 11, 2016·American Journal of Surgery·Yu-Yao ChangShih-Ching Chang

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Methods Mentioned

BETA
PCR

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SPSS

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