Tumor Location Is Associated With the Prevalence of Braf And Pik3ca Mutations in Patients with Wild-Type Ras Colorectal Cancer: A Prospective Multi-Center Cohort Study in Japan

Hiroya Taniguchi, Keisuke Uehara, Goro Nakayama, Hiroshi Nakayama, Toshisada Aiba, Norifumi Hattori, Masato Kataoka, Yasuyuki Nakano, Yoshihisa Kawase, Osamu Okochi, Hiroshi Matsuoka, Setsuo Utsunomiya, Eiji Sakamoto, Yoshinori Mori, Shinichi Umeda, Toshio Shikano, Koji Komori, Masahiro Tajika, Shigenori Kadowaki, Kei MuroYasushi Yatabe

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Primary tumor location is a critical prognostic factor that also impacts the efficacy of anti-epidermal growth factor receptor (EGFR) therapy in wild-type RAS (KRAS/NRAS) metastatic colorectal cancer (CRC). However, the association between the incidence of BRAF and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations and primary tumor location remains unclear. METHODS: We prospectively collected tumor samples and clinical data of patients from 15 hospitals between August 2014 and April 2016 to investigate RAS, BRAF, and PIK3CA mutations using a polymerase chain reaction-based assay. According to the primary tumor location, patients were classified to right-sided (from cecum to splenic flexure) and left-sided (from descending colon to rectum) tumor groups. RESULTS: In total, 577 patients with CRC were investigated, 331 patients (57%) had CRC with wild-type RAS; of these 331 patients, 10.5%, 4.8%, and 5.9% patients harbored BRAFV600E, BRAFnon-V600E, and PIK3CA mutations, respectively. BRAF/PIK3CA mutations were more frequent in females, patients with right-sided tumors, and patients with peritoneal metastasis cases and less frequent in patients with liver metastases. The prevalence rates of BRAFV600E and PIK3CA mutations were higher in patients with right-sided tumors than in those with left-sided tumors (32.3% vs. 4.8% and 17.2% vs. 3.6%, respectively). CONCLUSIONS: More than half of the patients with right-sided CRC and wild-type RAS harbored BRAF/PIK3CA mutations, including BRAFnon-V600E, which may contribute to the difference in the anti-EGFR efficacy between the right- and left-sided CRC.

Original languageEnglish
Article number100786
JournalTranslational Oncology
Volume13
Issue number7
DOIs
Publication statusPublished - 07-2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Taniguchi, H., Uehara, K., Nakayama, G., Nakayama, H., Aiba, T., Hattori, N., Kataoka, M., Nakano, Y., Kawase, Y., Okochi, O., Matsuoka, H., Utsunomiya, S., Sakamoto, E., Mori, Y., Umeda, S., Shikano, T., Komori, K., Tajika, M., Kadowaki, S., ... Yatabe, Y. (2020). Tumor Location Is Associated With the Prevalence of Braf And Pik3ca Mutations in Patients with Wild-Type Ras Colorectal Cancer: A Prospective Multi-Center Cohort Study in Japan. Translational Oncology, 13(7), [100786]. https://doi.org/10.1016/j.tranon.2020.100786