Infrequent CDKN2 mutation in human differentiated thyroid cancers.
We examined the frequency of cyclin-dependent kinase (CDK) N2 alterations in differentiated and anaplastic thyroid cancers to assess the involvement of CDKN2 in the development of these cancers. The CDKN2 gene, which encodes the cell-cycle regulator p16, was recently shown to be mutated or deleted in many tumor cell lines. Its role in the genesis of primary tumors is uncertain, however. Tumor and corresponding normal DNAs were prepared by microdissection of paraffin-embedded tissue blocks or from frozen surgical specimens of 15 papillary, 15 follicular, and five anaplastic thyroid carcinomas. The entire CDKN2 coding region was screened by single-strand conformational variant analysis and direct sequencing of variants. The presence of homozygous deletions was evaluated by multiplex polymerase chain reaction (PCR) analysis. Loss of heterozygosity (LOH) in the CDKN2 region was assessed by using flanking polymorphic markers. Two somatic missense mutations were found among the 35 thyroid cancers, one in a follicular tumor and one in an anaplastic tumor. Multiplex PCR suggested the presence of homozygous deletion in one anaplastic tumor and hemizygous deletions in four tumors. LOH studies revealed loss of 9p sequences in four follicular (27%) and two anaplastic (50%) cancers. Our data suggest that alterations in CDKN2 played a role in a minority of thyroid cancers (three of 35). LOH in the region of CDKN2 is seen in a significant proportion of follicular and anaplastic but not papillary cancers. Loss of 9p sequences suggests a role for a tumor suppressor gene in the development of follicular and anaplastic thyroid cancers.
Tung
W S
WS
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Shevlin
D W
DW
Bartsch
D
D
Norton
J A
JA
Wells
S A
SA
Goodfellow
P J
PJ
D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D017384:Sequence Deletion; D013964:Thyroid Neoplasms / Q000235:genetics*
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004273:DNA, Neoplasm