p16INK4 and p15INK4B alterations in primary gynecologic malignancy.
Chromosome 9 abnormalities have been found in primary tumors and cell lines from human gynecologic malignancy. Alterations of p16INK4 and p15INK4B genes mapped on the band p21 of chromosome 9 have been detected in various human tumors, but the role of these genes as tumor suppressors in vivo appear to be dependent on tumor type. Polymerase chain reaction (PCR)-based analysis was performed to search for lesions of these genes in 202 primary gynecologic malignancies. Homozygous deletions of p16INK4 were detected in 7 of 128 (5%) cervical, 1 of 41 (2%) endometrial, 2 of 27 (7%) ovarian, and 3 of 6 (50%) vulvar carcinomas, while homozygous deletions of p15INK4B were detected in 19 of 128 (15%) cervical, 1 of 41 (2%) endometrial, 9 of 27 (33%) ovarian, and 3 of 6 (50%) vulvar carcinomas, respectively. No mutations were found in exon 2 of p16INK4 from 161 cases of gynecologic malignancy without deletion of p16INK4. All 3 cases of vulvar carcinoma showing homozygous deletions of p16INK4 and p15INK4B were at advanced clinical stage (stage III-IV), while all 7 cases of cervical carcinoma and 2 cases of ovarian carcinoma showing homozygous deletion of p16INK4 were at early stage (stage I-II). The results indicate that homozygous deletions of p16INK4 and/or p15INK4B genes may play a role in a subset of primary gynecologic malignancy.
Wong
Y F
YF
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, N.T.
Chung
T K
TK
Cheung
T H
TH
Nobori
T
T
Yim
S F
SF
Lai
K W
KW
Phil
M
M
Yu
A L
AL
Diccianni
M B
MB
Li
T Z
TZ
Chang
A M
AM
D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D005833:Genital Neoplasms, Female / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins