The cytogenetic studies in melanoma of this application, indicate that alterations of chromosome 1 are one of the most frequent anomalies of melanoma and that chromosome breaks frequently cluster at band region 1p36. The PITSLRE gene locus maps to band region 1p36 and appears to be involved in apoptotic signaling. Initial studies in their laboratory indicate alterations in PITSLRE gene copies and abnormal PITSLRE protein expression in melanoma. It was hypothesized that alterations in the PITSLRE gene locus on chromosome and 1p36 are involved in melanoma pathogenesis, possibly by disrupting apoptotic signaling pathways and preventing the elimination of tumor cells through normal checkpoint control. To test this hypothesis they proposed the following specific aims: 1) to determine if the PITSLRE genes are deleted in melanoma cell- lines with chromosome 1p alterations; 2) to analyze PITSLRE expression in melanoma cell lines and primary melanoma; 3) to determine the frequency of PITSLRE gene alterations in primary melanoma specimens; and 4) to determine whether PITSLRE genes play a function role in suppressing growth and/or tumorigenicity of melanoma cell lines.
