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Poster display

3891 - Clinical characteristics in colorectal cancer harboring BRAF V600E and non-V600E mutations

Date

10 Oct 2016

Session

Poster display

Presenters

Eiji Shinozaki

Citation

Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363

Authors

E. Shinozaki1, Y. Miki2, M. Ueno3, M. Igarashi4, K. Chin1, D. Takahari1, M. Ogura1, T. Ichimura1, I. Nakayama1, H. Osumi1, T. Wakatsuki1, T. Matsushima1, K. Yamaguchi1

Author affiliations

  • 1 Department Of Gi Oncology, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 2 Lab Of Genetic Diagnosis, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 3 Department Of Gastroenterological Surgery, Cancer Institute Hospital of JFCR, Tokyo/JP
  • 4 Department Of Gastroenterology, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
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Abstract 3891

Background

BRAF V600E mutation (MT) in metastatic colorectal cancer (CRC) has been known thoroughly as a prognostic biomarker, and as a negative predictive biomarker for anti-EGFR treatment. On the other hand, the feature of BRAF MTs other than BRAF V600E still remains unclear. This study aimed to reveal the clinical characteristics of BRAF non-V600E MTs compared with the EGFR signaling pathway MTs status including BRAF V600E MT.

Methods

Consecutive patients from June 2012 to November 2013 were enrolled in this study. Multiplex genotyping of EGFR signaling pathway was performed on archival samples using Luminex Assay (MABGEN, GENOSEARCH Mu-PACK and GENOSEARCH BRAF, MBL) for BRAF V600E / BRAFnon-V600E, KRAS including exon 2, 3 and 4, NRAS, and PIK3CA. We analyzed the correlation among MTs profile, clinical data and location of CRC.

Results

A total of 824 CRC patients was analyzed; consisted of 374 females and 450 males, 147, 200, 263 and 214 in stage I, II, III and IV or recurrent CRC, respectively. The incidence of MTs were as followings; BRAF V600E / BRAFnon-V600E, KRAS including exon 2, 3 and 4, NRAS and PIK3CA were 5.3% / 1.7%, 41.5%, 3.3% and 9.7%, respectively. The relationship among main characteristics and mutational status showed in table below. Although RAS and BRAF V600E MTs were in a mutually exclusive manner, one case of co-mutation with KRAS A146T MT was observed in BRAFnon-V600E cases. In both BRAFV600E MT and BRAFnon-V600E MT, four cases were having co-mutation with PIK3CA MTs.

female/ male n = 374/ 450 right/ left +rectum* n = 235/ 589 (335 + 254) por/ others** n = 47/ 777 stage I/ II/ III/ IV + rec*** n = 147/ 200/ 263/ 214
BRAFV600E n = 44 24/ 20 33/ 11 (8 + 3) 9/ 35 7/ 11/ 9/ 17
BRAFnon-V600E n = 14 7/ 7 3/ 11 (4 + 7) 1/ 13 4/ 4/ 3/ 3
KRAS exon2 n = 307 153/ 154 116/191(89 + 102) 9/ 298 52/ 76/ 102/ 65
KRAS exon3,4 n = 35 17/ 18 4/ 31 (16 + 15) 2/ 33 6/ 6/ 17/ 5
NRAS n = 27 13/ 14 2/ 25 (11 + 14) 0/ 27 2/ 7/ 8/ 9
PIK3CA n = 80 32/ 48 38/ 42 (17 + 25) 2/ 78 15/ 25/ 23/ 17

Abbreviation; *right/ left-sided colon; ** poorly differentiate; *** recurrence

Conclusions

In this analysis BRAFnon-V600E MTs were identified as a rare fraction and had no specific character revealed in contrast to the BRAFV600E MT, which was more frequent in right-sided primary, female and poorly differentiated histology. Further more large-scale investigation in this rare fraction of BRAFnon-V600E MTs will be necessary to clarify its clinical meaning for precision medicine.

Clinical trial identification

none

Legal entity responsible for the study

N/A.

Funding

Japanese Foundation for Cancer Research

Disclosure

All authors have declared no conflicts of interest.

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