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.
|Tumor||cMET Mutation||Secondary Mutations|
|Colorectal Adeno||N375S, R988C, T1010I, Y1248H, Y1253D||P53, KRAS, PI3K|
|Melanoma||N375S, T1010I||NRAS, BRAF|
|Lung Adeno||N375S||EGFR, KRAS|
|Thyroid Ca.||N375S, T1010I||P53, BRAF, PI3K|
|Ovarian Ca.||N375S, T1010I||P53|
|Breast Ductal Ca.||N375S||PI3K|
|SCC of H&N||N375S, R988C, T1010I||PI3K|