5011 Background: Cervical adenocarcinomas (AC) have higher rates of recurrence and distant metastasis, compared with squamous cell carcinomas (SCC), and decreased survival in advanced disease. Yet, tailored treatments for cervical cancers have not emerged. The aim of this study was to compare the frequency and type of somatic mutations in cervical AC and SCC to identify novel therapeutic targets for both subtypes. Methods: Tumors from 61 patients with cervical cancer (36 AC, 25 SCC) underwent genomic profiling by OncoMap, a multiplexed mass spectrometric genotyping technology that interrogates more than 400 known mutations in 33 cancer genes. Results: Overall, 31/61 (50.8%) tumors harbored candidate mutations, and 6/61 (9.8%) had ≥2 mutations. PIK3CA mutations were present in 21/64 (34.4%) of cervical cancers, with a trend towards higher rates in SCC compared with ACC (21/25 or 48.0% vs. 9/27 or 33.3%, p=0.10). KRAS mutations were present in 6/31 (16.7%) of AC, but none of the SCC (0%; 0/25). EGFR mutations were present in 9/25 (36.0%) of SCC, including G719S, but none of AC (0%; 0/31). Conclusions: The identification of distinct genomic alterations in SCC and AC of the cervix suggest different therapeutic rationales for each subtype. EGFR amplification in cervical SCC has been previously reported, but this is the first identification, to our knowledge, of activating EGFR mutations in cervical SCC. Together, this suggests that EGFR-inhibitors might be useful in selected patients with cervical SCC. Similarly, activating mutations in KRAS and PIK3CA in AC suggest that inhibition of the MAPK pathway (MEK inhibitors) and/or PI3K pathway may be beneficial in this subtype. Future studies should include more comprehensive genomic profiling strategies, such as targeted massively parallel sequencing, to detect multiple types of genomic alterations.
KRAS Mutations in Squamous Cell Carcinomas of the Lung
