A methylthioadenosine phosphorylase (MTAP) fusion transcript identifies a new gene on chromosome 9p21 that is frequently deleted in cancer

Homozygous deletions of human chromosome 9p21 occur frequently in malignant cell lines, and are also common in primary gliomas, lung cancers, and leuk emias. Moving from the centromere to the telomere, this complex region enco des the tumor suppressor genes p15(INK4B) (CDKN2B), p14(ARF), P16(INK4A) (C DKN2A), and the housekeeping gene methylthioadenosine phosphorylase (MTAP). However, not all chromosome 9p21 deletions in tumors include these tumor s uppressor genes. Here we describe the partial sequence and the exact locali zation of a nerv gene on chromosome 9p21 centromeric of p15(INK4B) that for med an in frame fusion transcript with MTAP in a glioma xenograft, and that is homozygously deleted in various malignant cell lines, Northern blot rev ealed corresponding 1.5 kb transcript in non-deleted cell lines as well as in normal lymphocytes, Using a RNA master blot membrane including 50 differ ent tissues, we could show that this new transcript is expressed in all tis sues of the adult but not or only at very low levels in most of the fetal t issues tested. The expression pattern is similar to that of p16(INK4A). The localization as well as the deletion pattern makes this transcript a candi date for a new tumor suppressor gene.