title: Identification of a novel candidate gene, CASC2, in a region of common allelic loss at chromosome 10q26 in human endometrial cancer.
abstract: 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.
authors.affiliation: Istituto di Anatomia Patologica, Università di Sassari, Via Matteotti, Sassari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Baldinu
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Antonella
authors.initials: A
authors.lastname: Manca
authors.forename: Maria P
authors.initials: MP
authors.lastname: Satta
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sini
authors.forename: Carla
authors.initials: C
authors.lastname: Rozzo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Dessole
authors.forename: PierLuigi
authors.initials: P
authors.lastname: Cherchi
authors.forename: Fernando
authors.initials: F
authors.lastname: Gianfrancesco
authors.forename: Adriana
authors.initials: A
authors.lastname: Pintus
authors.forename: Annangela
authors.initials: A
authors.lastname: Carboni
authors.forename: Angelo
authors.initials: A
authors.lastname: Deiana
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002879:Chromosomes, Human, Pair 10; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D012333:RNA, Messenger / Q000378:metabolism; D017421:Sequence Analysis; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C484713:long non-coding RNA CASC2, human