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Mechanism of inactivation of CDKN2 and MTS2 in non-small cell lung cancer and association with advanced stage.

Publication ,  Journal Article
Nakagawa, K; Conrad, NK; Williams, JP; Johnson, BE; Kelley, MJ
Published in: Oncogene
November 2, 1995

The CDKN2 tumor suppressor gene encodes an inhibitor of type D cyclin dependent kinases. CDKN2 is homozygously deleted in approximately 25% of nonsmall cell lung cancer (NSCLC) cell lines and these deletions are associated with advanced stage cancer. Conflicting reports of the frequency of CDKN2 alterations in NSCLC tumors prompted us to examine the relationship of these alterations and those of the related gene, MTS2, with patient stage and site of cancer. One hundred twenty-five NSCLC samples (71 cell lines and 54 tumors) were examined by PCR-SSCP. Twenty of 71 (28%) tumor cell lines had homozygous deletions, and six (8%) had point mutations compared to 4 (7%) with point mutations among 54 tumor samples. All mutations were observed in tumors or cell lines from patients with stage III or IV disease. Two patients with no mutations in their primary tumor had a CDKN2 point mutation detected in a metastatic tumor. Point mutations were G:C to T:A transversion on the coding strand in five of 10 and resulted in nonsense mutations in seven of 10. Undetectable CDKN2 mRNA, in the absence of detectable genetic alteration, was noted in a similar fraction of cell lines derived from patients with stage I or II disease [two of seven (29%)] and stage III or IV disease [15 of 49 (31%)]. Homozygous deletion of MTS2 was found in 17 of 20 cell lines with CDKN2 deletions; no point mutations of MTS2 were identified by SSCP in the 125 samples. Thus, CDKN2 is a frequent target of genetic alterations at 9p21 in NSCLC. Both deletions and point mutations of CDKN2 are closely associated with tumor dissemination.

Duke Scholars

Published In

Oncogene

ISSN

0950-9232

Publication Date

November 2, 1995

Volume

11

Issue

9

Start / End Page

1843 / 1851

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Cells, Cultured
  • RNA, Messenger
  • Polymorphism, Single-Stranded Conformational
  • Polymerase Chain Reaction
  • Point Mutation
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Neoplasm Metastasis
  • Molecular Sequence Data
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nakagawa, K., Conrad, N. K., Williams, J. P., Johnson, B. E., & Kelley, M. J. (1995). Mechanism of inactivation of CDKN2 and MTS2 in non-small cell lung cancer and association with advanced stage. Oncogene, 11(9), 1843–1851.
Nakagawa, K., N. K. Conrad, J. P. Williams, B. E. Johnson, and M. J. Kelley. “Mechanism of inactivation of CDKN2 and MTS2 in non-small cell lung cancer and association with advanced stage.Oncogene 11, no. 9 (November 2, 1995): 1843–51.
Nakagawa K, Conrad NK, Williams JP, Johnson BE, Kelley MJ. Mechanism of inactivation of CDKN2 and MTS2 in non-small cell lung cancer and association with advanced stage. Oncogene. 1995 Nov 2;11(9):1843–51.
Nakagawa, K., et al. “Mechanism of inactivation of CDKN2 and MTS2 in non-small cell lung cancer and association with advanced stage.Oncogene, vol. 11, no. 9, Nov. 1995, pp. 1843–51.
Nakagawa K, Conrad NK, Williams JP, Johnson BE, Kelley MJ. Mechanism of inactivation of CDKN2 and MTS2 in non-small cell lung cancer and association with advanced stage. Oncogene. 1995 Nov 2;11(9):1843–1851.

Published In

Oncogene

ISSN

0950-9232

Publication Date

November 2, 1995

Volume

11

Issue

9

Start / End Page

1843 / 1851

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Cells, Cultured
  • RNA, Messenger
  • Polymorphism, Single-Stranded Conformational
  • Polymerase Chain Reaction
  • Point Mutation
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Neoplasm Metastasis
  • Molecular Sequence Data