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The location of colorectal cancer (right- vs. left-sided colon and rectum) affects the prevalence of BRAF V600E, non-V600E and PIK3CA mutations: a prospective registration study in the Aichi Cancer Network

Date

08 Oct 2016

Session

Poster Display

Presenters

Hiroya Taniguchi

Citation

Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370

Authors

H. Taniguchi1, K. Uehara2, H. Nakayama3, G. Nakayama4, T. Takahashi5, Y. Nakano6, H. Matsuoka7, S. Utsunomiya8, E. Sakamoto9, Y. Mori10, K. Komori11, M. Tajika12, K. Muro1, Y. Yatabe13

Author affiliations

  • 1 Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 2 Department Of Surgical Oncology, Nagoya University, Graduate School of Medicine, Nagoya/JP
  • 3 Department Of Surgery, National Hospital Organization, Nagoya Medical Center, Nagoya/JP
  • 4 Department Of Gastroenterological Surgery, Nagoya University, Graduate School of Medicine, Nagoya/JP
  • 5 Department Of Surgery, Tosei General Hospital, Seto/JP
  • 6 Department Of Medical Oncology, Japanese Red Cross Nagoya First Hospital, 464-8681 - Nagoya/JP
  • 7 Surgery, Fujita Health University, Toyoake/JP
  • 8 Deparment Of Medical Oncology, Kainan Hospital, Yatomi-shi/JP
  • 9 Department Of Surgery, Japanese Red Cross Nagoya Daini Hospital, Nagoya/JP
  • 10 Department Of Gastroenterology And Metabolism, Nagoya City University, Nagoya/JP
  • 11 Department Of Gatsroenterological Surgery, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 12 Depaerment Of Endoscopy, Aichi Cancer Center Hospital, 4648681 - Nagoya/JP
  • 13 Department Of Clinical Oncologydepartment Of Pathology And Molecular Diagnostics, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
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Resources

Abstract 2783

Background

Primary tumor location is an important predictive factor for KRAS/NRAS wild-type colorectal cancer treated with anti-EGFR therapy. BRAF and PIK3CA mutations are also known to affect a response in anti-EGFR therapy. However, the relationship between the prevalence of BRAF/PIK3CA mutations and the location of the primary site is still unclear.

Methods

We prospectively collected tumor samples and clinical data from colorectal cancer patients in 14 hospitals and investigated KRAS/NRAS/BRAF/PIK3CA gene mutations, including 33 types of BRAF non-V600E mutations, using a PCR-based multiplex kit.

Results

As of April 30, 2015, a total of 545 CRC patients were enrolled, and 313 patients (57%) revealed KRAS/NRAS wild-type cancer. Patient characteristics included: median age, 65 (range, 30–90); male/female, 60%/40%; clinical stage I-III/IV, 15%/85%; and location of primary site, right-sided colon/left-sided colon/rectum, 23%/30%/47%. The prevalence of BRAF V600E/BRAF non-V600E/PIK3CA mutations were 10.1%, 4.7% and 5.9%, respectively. The detected BRAF non-V600E mutations were G466E, G469A, N581T, D594G, T599_V600insT, V600R, K601E and K601N. All mutations were mutually exclusive. In RAS wild-type cancer patients, BRAF/PIK3CA mutations were more frequent in female (p = 0.0029), right-sided (p = 0.0001) and peritoneal metastasis (p = 0.0016) cases and less frequent in cases presenting liver metastasis (p = 0.0041). In RAS wild-type right-sided cancers, the prevalence of BRAF V600E/ BRAF non-V600E/PIK3CA mutations were 31.7%, 8.1% and 19.2%, while in left-sided colon and rectum cancers, they were 4.6%, 2.5% and 3.6%, respectively.

Conclusions

More than half of RAS wild-type right-sided colon cancer patients have BRAF/PIK3CA mutations, including BRAF non-V600E. The existence of these mutations may affect anti-EGFR efficacy between right- and left-sided colorectal cancers.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

Aichi Cancer Network

Disclosure

All authors have declared no conflicts of interest.

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