Presence of RAS mutations but no role of BRAF and beta-catenin mutations together with human papilloma virus (HPV) in squamous cell carcinoma of esophagus in a high-risk population from Kashmir.

B188

Worldwide esophageal cancer ranks among the ten most common cancers. Although, there is a rising entity of adenocarcinoma, the majority of carcinoma of the esophagus are squamous-cell carcinoma. It shows uneven geographical distribution in its occurrence, reflecting the influence of local environmental conditions, lifestyle and genetic predisposition in the development of the cancer. Kashmir valley, in the north of India, has been described as a high-risk area for esophageal squamous cell carcinoma (ESCC). In the present investigation an attempt was made to study polymorphisms in oncogenes viz., KRAS, NRAS, BRAF and beta-catenin in 47 ESCC patients from Kashmir valley. The hot spot mutation regions of KRAS, NRAS, BRAF and beta-catenin were analyzed in matched tumor and normal tissues using a combination of PCR-SSCP and direct sequencing. None of the tumors showed the presence of commonly reported mutations in either BRAF or beta-catenin but our analysis indicated the presence of mutations in RAS (NRAS- exon 2; 4/47 and KRAS- exon 1; 1/47). In view of the fact that HPV has been linked to pathogenesis of esophageal cancer, we screened for presence of HPV in all the tumors. We used two different sets of consensus primers viz., GP5+ and GP6+; PGMY09 and PGMY11 in conjunction with reverse line blot assay to screen for HPV. Interestingly we did not detect HPV in any of the specimens. In conclusion our results suggest that squamous cell carcinoma of esophagus in Kashmir may arise independent of oncogenic BRAF and beta-catenin mutations but RAS mutations most likely play a role in the pathogenesis of ESCC. Moreover, in our present study HPV is unlikely to be an etiologic factor for ESCC in this region.