Frequent homozygous deletion of cyclin-dependent kinase inhibitor 2 (MTS1, p16) in superficial bladder cancer detected by fluorescence in situ hybridization.
Deletion of all or part of chromosome 9 is a well-described genetic alteration in bladder tumors. It has been proposed that inactivation of a tumor-suppressor gene on chromosome 9 is an important event in tumor development. Recent reports have supported cyclin-dependent kinase inhibitor 2 (CDKN2, also known as MTS1, INK4, p16) at 9p21 as a candidate tumor-suppressor gene in solid tumors. However, the prevalence of CDKN2 mutations in primary bladder tumors has been controversial. Therefore, we applied gene-specific probes for CDKN2 and the interferon alpha gene (IFNA), also located at 9p21, to characterize further the genomic deletions at this locus in bladder cancer. Seventeen superficial (pTa or pT1) bladder tumor specimens were examined for gene deletion by fluorescence in situ hybridization. Dual-labeling hybridization with a repetitive pericentromeric probe for chromosome 9 and a gene-specific probe for CDKN2 was performed to characterize the gene copy number in relation to the chromosome 9 copy number on a cell-by-cell basis. Homozygous deletion for CDKN2 without homozygous IFNA deletion was found in 5 of 17 tumors tested. Both genes were deleted in one additional case, and one tumor showed deletion of IFNA without deletion of CDKN2. Homozygous deletion at the 9p21 locus was found only in tumors having monosomy for the chromosome 9 centromeric signal. These results indicate that the homozygous deletion of the CDKN2 gene is a frequent and early event in superficial bladder cancer.
Balázs
M
M
Department of Laboratory Medicine, University of California San Francisco 94143-0808, USA.
Carroll
P
P
Kerschmann
R
R
Sauter
G
G
Waldman
F M
FM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D002872:Chromosome Deletion; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases