title: High-resolution genotyping of chromosome 8 in colon adenocarcinomas reveals recurrent break point but no gene mutation in the 8p21 region.
abstract: The prognosis of patients with colorectal cancer is largely determined by the tumor stage. In this respect, colorectal cancer with lymph node metastases has the worst prognosis. Accordingly, there is considerable clinical interest in understanding the genetic mechanisms underlying metastasis formation. The short arm of chromosome 8 is often lost in colorectal cancer and has been associated with the advanced stages. A common region of deletion has been identified in 8p21, and we investigate here the localization of the putative tumor suppressor gene. A series of 683 sporadic microsatellite stability colorectal tumor samples has been genotyped on 12 microsatellite loci encompassing the common deleted region. Allelic losses were identified in 50% of the cases and 10 break points have been evidenced between D8S1734 and D8S1810, reducing the region of interest to D8S1771-D8S131. Among the 21 genes mapped in this interval, 14 candidate genes have been retained for the sequencing analysis of 48 tumors with 8p allelic loss. No mutation was found, suggesting more complex mechanisms of inactivation or side effects of chromosome arm 8q duplication, which might be up-regulating oncogenes not located within the deleted region.
authors.affiliation: CHU St-Antoine, Department of Pathology, Paris, France.
authors.forename: Najat
authors.initials: N
authors.lastname: Mourra
authors.forename: Guy
authors.initials: G
authors.lastname: Zeitoun
authors.forename: Guillaume
authors.initials: G
authors.lastname: Portier
authors.forename: Hélène
authors.initials: H
authors.lastname: Blanche
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tubacher
authors.forename: Laetitia
authors.initials: L
authors.lastname: Gressin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Flejou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tiret
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D043171:Chromosomal Instability; D019457:Chromosome Breakage; D043283:Chromosome Fragile Sites; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm