Cloning of a human ortholog (RPH3AL) of (RNO)Rph3al from a candidate 17p13.3 medulloblastoma tumor suppressor locus

Allelic loss of 17p13.3 is observed in approximately 40% of medulloblastoma s, suggesting the presence of a tumor suppressor gene in this region. Delet ion mapping has defined a region of common loss flanking the telomeric mark er D17S34, and a recent report delineated a 9-kb homozygous deletion within the D17S34 locus in one such tumor. Using cDNA selection, we have identifi ed a transcript spanning this deletion, designated (HSA)RPH3AL (rabphillin- 3A-like), based on its 77% overall amino acid identity with a recently clon ed rat gene, (RNO)Rph3al (originally termed Noc2), a gene putatively involv ed in regulated endocrine exocytosis through its interactions with the cyto skeleton. We determined the exon-intron boundaries of RPH3AL and screened t he coding region for mutations by direct sequencing in DNA extracted from 3 3 tumor samples with allelic loss of 17p13, including 10 medulloblastoma, 1 4 follicular thyroid cancer (FTC), and 9 ovarian cancer specimens. No mutat ions were identified. Thus, despite its location in a homozygously deleted 17p13.3 locus, it is unlikely that RPH3AL is a gene involved in the oncogen esis of medulloblastoma, FTC, or ovarian cancer, (C) 1999 Academic Press.