KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study.

Abstract

BACKGROUND:

Inhibitors of the epidermal growth factor (EGFR) signaling pathway have a major role in the treatment of KRAS wild-type colorectal cancer patients. The EGFR pathway has been shown to be activated in gastric cancer (GC). However, published data on KRAS and BRAF mutation status is limited in GC and has not been compared between GC from different geographic regions.

METHODS:

The prevalence of KRAS and BRAF mutations was established in 712 GC: 278 GC from the United Kingdom, 230 GC from Japan and 204 GC from Singapore. The relationship between KRAS/BRAF mutation status, DNA mismatch repair (MMR) status, clinicopathological variables and overall survival was analysed.

RESULTS:

Overall, 30 (4.2%) GC carried a KRAS mutation. In total, 5.8% of the UK GC, 4% of Japan GC and 1.5% of Singapore GC were KRAS mutant. KRAS mutant GC had fewer lymph node metastases in the UK cohort (P=0.005) and were more frequent in elderly patients in the Japan cohort (P=0.034). KRAS mutations were more frequent in MMR-deficient GC in the UK and the Japanese cohort (P<0.05). A BRAF mutation was only detected in a single Japanese GC.

CONCLUSIONS:

This large multicentre study demonstrated that KRAS mutations and DNA MMR deficiency have a role in a small subgroup of GC irrespective of country of origin, suggesting that this subgroup of GC may have developed along a common pathway. Further studies need to establish whether concomitant mutations or amplifications of other EGFR signalling pathway genes may contribute to the activation of this pathway in GC.

• Authors: N C T van Grieken, T Aoyama, T Aoyma, P A Chambers, D Bottomley, L C Ward, I Inam, T E Buffart, K Das, T Lim, B Pang, S L Zhang, I B Tan, B Carvalho, D A M Heideman, Y Miyagi, Y Kameda, T Arai, G A Meijer, A Tsuburaya, P Tan, T Yoshikawa, H I Grabsch
• Journal: British journal of cancer (Br J Cancer) Vol. 108 Issue 7 Pg. 1495-501 (Apr 16 2013) ISSN: 1532-1827 [Electronic] England
• PMID: 23511561 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• KRAS protein, human
• Proto-Oncogene Proteins
• ErbB Receptors
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Proto-Oncogene Proteins p21(ras)
• ras Proteins

Topics

• Aged
• Cohort Studies
• DNA Mismatch Repair
• DNA Repair-Deficiency Disorders
• ErbB Receptors (genetics)
• Female
• Genes, ras
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Mutation
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins B-raf (genetics)
• Proto-Oncogene Proteins p21(ras)
• Stomach Neoplasms (enzymology, genetics)
• ras Proteins (genetics)