[1861] cMET Mutations, Co-Mutations, and Survival Outcome

Maryam Zenali, Zesheng Liu, Zhuang Zuo, Russell Broaddus. University of Vermont, Burlington, VT; University of Texas MD Anderson Cancer Center, Houston, TX

Background: Proto-oncogene cMET and its ligand, HGF, are involved in survival & motility. Both mutation & overexpression of cMET gene have been found associated with driving tumorigenesis. There is also emerging evidence that some cMET mutations may be genetic polymorphisms. This study summarizes types of cMET mutations and rate of comutations with other genes in different tumors, including metastatic colorectal cancer (mCRC).
Design: We reviewed 1500 cases with panel mutation test (13 genes including KRAS, BRAF, EGFR and cMET), 47 cases had cMET mutations. In this group, SNPs, their distribution in tumor types, and incidence of comutations with other genes were recorded. mCRC was the largest tumor category harboring only cMET mutation. Survival outcome was determined for mCRCs with only cMET mutation (n=14) versus mCRC with no mutations (n=24).
Results: cMET point mutations were at five codons: 66 % N375S; 21% T1010I, and remaining: R988C & Y1248H & Y1253D. 50% of tumors with cMET mutation had mutation of at least one other gene in the panel. None of the cases with cMET mutation had amplification by FISH. Survival of the CRC patients with only cMET mutation was better than those without cMET mutation,not significant (p=0.057). Table 1 & figure 1.

cMET mutations & co-mutations
TumorcMET MutationSecondary Mutations
Colorectal AdenoN375S, R988C, T1010I, Y1248H, Y1253DP53, KRAS, PI3K
MelanomaN375S, T1010INRAS, BRAF
Lung AdenoN375SEGFR, KRAS
Thyroid Ca.N375S, T1010IP53, BRAF, PI3K
Ovarian Ca.N375S, T1010IP53
Breast Ductal Ca.N375SPI3K
SCC of H&NN375S, R988C, T1010IPI3K
Prostatic AdenoN375SP53





Conclusions: Incidence of comutations in tumors with cMET mutation is 50%, indicating a high probability of escape pathways in tumors harboring these mutations; this should be considered when therapeutically targeting cMET. Outcome in mCRC was not adversely affected by cMET mutation when excluding cases with comutations, suggesting that these may represent polymorphisms. A larger study is needed to further assess this concept.
Category: Pathobiology

Monday, March 4, 2013 1:00 PM

Poster Session II # 268, Monday Afternoon

 

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