Frequent p16INK4 (MTS1) gene inactivation in testicular germ cell tumors.
The molecular mechanisms responsible for the development of testicular germ cell tumors (GCTs) have not as yet been elucidated. The aim of the present study was to determine whether genetic alterations of p16INK4 (MTS1) and/or cyclin-dependent kinase 4 (CDK4) occur in the genesis of these tumors. We have analyzed these two genes in 29 testicular GCTs, seminomas, and nonseminomas. None of the tumors showed either p16INK4 or CDK4 mutations. Only 1 of the 29 GCTs displayed loss of heterozygosity of the p16INK4 gene. No homozygous deletions of p16INK4 were detected. Evidence of hypermethylation of p16INK4 exon 1, however, was demonstrated in 13 of the 26 (50%) GCTs analyzed. Tumor samples having exon 1 of p16INK4 methylated expressed significantly lower levels of p16INK4 mRNA, as analyzed by reverse transcriptase polymerase chain reaction. These results suggest that p16INK4 inactivation plays a role in the genesis of GCTs.
Chaubert
P
P
Institut Universitaire de Pathologie, CHUV, Lausanne, Switzerland.
Guillou
L
L
Kurt
A M
AM
Bertholet
M M
MM
Metthez
G
G
Leisinger
H J
HJ
Bosman
F
F
Shaw
P
P
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013736:Testicular Neoplasms / Q000235:genetics*; D025803:Tumor Suppressor Protein p14ARF
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011506:Proteins; D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF