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Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines.

Publication ,  Journal Article
Terry, LA; Boyd, J; Alcorta, D; Lyon, T; Solomon, G; Hannon, G; Berchuck, A; Beach, D; Barrett, JC
Published in: Mol Carcinog
August 1996

p21/WAF1/CIP1/SDI1 is an important cell-cycle mediator with tumor suppressor gene capabilities, and its inactivation could potentially lead to tumor progression. Because tumor suppressor genes are commonly inactivated by somatic and germline mutations, we analyzed a variety of human tumor cell lines for p21 mutations. We used single-strand conformational analysis and direct sequencing to identify possible mutations in the p21 coding region. Two base-alterations were observed in 41 immortalized human tumor cell lines. A previously reported polymorphism that results in a serine-to-arginine amino-acid substitution at codon 31 was found in 24% (10 of 41) of the tumor cell lines but was also found in 10% (six of 62) of normal parental DNAs tested and 7% (three of 43) of normal DNAs from patients with primary endometrial tumors. Another nucleotide substitution found at codon 80 resulted in the replacement of threonine with methionine. Codon 80 changes were found in 7% (three of 41) of the tumor cell lines (all endometrial) and in 2% (one of 62) of the normal parental DNAs. This change was not found in any of the primary endometrial tumors examined. The biological activity of these base changes was analyzed by using in vitro cyclin-dependent kinase 2-cyclin A kinase assays and calcium phosphate transfections. We observed that wild-type p21 and the p21 variants had similar growth-inhibitory abilities. Thus, our results suggest that mutation of the p21 gene is not prevalent in human tumor cell lines and is not a probable mechanism of inactivation of this gene.

Duke Scholars

Published In

Mol Carcinog

DOI

ISSN

0899-1987

Publication Date

August 1996

Volume

16

Issue

4

Start / End Page

221 / 228

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Polymorphism, Genetic
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mutation
  • Molecular Sequence Data
  • Humans
  • DNA, Neoplasm
  • DNA Mutational Analysis
  • Cyclins
 

Citation

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MLA
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Terry, L. A., Boyd, J., Alcorta, D., Lyon, T., Solomon, G., Hannon, G., … Barrett, J. C. (1996). Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines. Mol Carcinog, 16(4), 221–228. https://doi.org/10.1002/(SICI)1098-2744(199608)16:4<221::AID-MC6>3.0.CO;2-I
Terry, L. A., J. Boyd, D. Alcorta, T. Lyon, G. Solomon, G. Hannon, A. Berchuck, D. Beach, and J. C. Barrett. “Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines.Mol Carcinog 16, no. 4 (August 1996): 221–28. https://doi.org/10.1002/(SICI)1098-2744(199608)16:4<221::AID-MC6>3.0.CO;2-I.
Terry LA, Boyd J, Alcorta D, Lyon T, Solomon G, Hannon G, et al. Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines. Mol Carcinog. 1996 Aug;16(4):221–8.
Terry, L. A., et al. “Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines.Mol Carcinog, vol. 16, no. 4, Aug. 1996, pp. 221–28. Pubmed, doi:10.1002/(SICI)1098-2744(199608)16:4<221::AID-MC6>3.0.CO;2-I.
Terry LA, Boyd J, Alcorta D, Lyon T, Solomon G, Hannon G, Berchuck A, Beach D, Barrett JC. Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines. Mol Carcinog. 1996 Aug;16(4):221–228.
Journal cover image

Published In

Mol Carcinog

DOI

ISSN

0899-1987

Publication Date

August 1996

Volume

16

Issue

4

Start / End Page

221 / 228

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Polymorphism, Genetic
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mutation
  • Molecular Sequence Data
  • Humans
  • DNA, Neoplasm
  • DNA Mutational Analysis
  • Cyclins