Identification of a novel candidate gene, CASC2, in a region of common allelic loss at chromosome 10q26 in human endometrial cancer

Allelic deletions, which are suggestive for the presence of tumor suppressor genes, represent a common event in endometrial Cancer (EC). Previous loss-of-heterozygosity studies for human chromosome 10q identified a candidate deletion interval at 10q25-q26, which we further narrowed to a 160-kb region at 10q26, bounded by markers D10S1236 and WIAF3299. Using a positional candidate approach, we identified three alternative transcripts of a novel human gene, CASC2 (Cancer susceptibility candidate 2; formely C10orf5). One of such transcripts, CASC2a, encodes a short protein of 102 Amino acids with no similarity to any Other known gene product. Three (7%) CASC2a mutations were identified in tumor DNA from 44 EC patients. While c.-156G>T and c.22C>T (p.Pro8Ser) are sequence variants with unknown functional significance, c.84delA is a mutation with a truncation effect on the predicted protein (p. Asn28fsX50). Expression studies by real-time RT-PCR on several normal and tumor cells revealed that CASC2a mRNA is downregulated in Cancer, suggesting that it may act as a potential tumor suppressor gene. The very low mutation rate seems to also indicate that inactivation of CASC2a might probably be due to mechanisms different from genetic alterations.