Identification of a 6-cM minimal deletion at 11q23.1-23.2 and exclusion of PPP2R1B gene as a deletion target in cervical cancer.
Previous functional and deletion mapping studies on cervical cancer (CC) have implicated one or more tumor suppressor genes (TSGs) on chromosome 11 at q13 and q22-24 regions. Of these, the 11q22-24 region exhibits frequent allelic deletions in a variety of solid tumor types, suggesting the presence of critical genes for tumor suppression in this region. However, the precise region of deletion on 11q is not clearly defined in CC. In an attempt to accurately map the deleted region, we performed an extensive loss of heterozygosity (LOH) mapping in 58 tumors using 25 polymorphic loci on both the short and long arms. The pattern of LOH identified three sites of deletions, two on 11p (p15.11-p15.3 and p12-13), and one on 11q (q23.1-q23.2). The 11q23.1-q23.2 exhibited highest frequency (60.6%) of deletions, suggesting that this could be the site of a candidate TSG in CC. The minimal deletion at 11q23.1-23.2 was restricted to a 6-cM region between 123.5 and 129.5 cM genetic distance on chromosome 11, identifying the site of a potential TSG important in the pathogenesis of CC. At least five known genes and 28 UniGene clusters were mapped to the present commonly deleted region. In addition, we have excluded a previously known TSG PPP2R1B at 11q23 as a deletion target in CC. The definition of the minimal deletion and the availability of expressed sequence resources should facilitate the identification of the candidate TSG.
Pulido
H A
HA
Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Fakruddin
M J
MJ
Chatterjee
A
A
Esplin
E D
ED
Beleño
N
N
Martinez
G
G
Posso
H
H
Evans
G A
GA
Murty
V V
VV
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002880:Chromosomes, Human, Pair 11; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
D010749:Phosphoprotein Phosphatases