Clonal origin of multiple lung cancers: K-ras and p53 mutations determined by nonradioisotopic single-strand conformation polymorphism analysis

Derick H Lau, Bangjie Yang, Ruide Hu, John R. Benfield

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Disease stage is the most important factor in determining prognosis and treatment of lung cancer. Staging of lung cancer is complicated by presentation of multiple pulmonary malignant lesions with a similar histology. It is a dilemma to decide if these lesions are synchronous primaries arising from different malignant clones or metastases from a single clone. Lung cancer is associated with multiple genetic abnormalities including mutations of K-ras and p53, which are believed to occur prior to onset of metastasis. To determine the clonal origin of multiple pulmonary malginant nodules, we analyzed point-mutations of K-ras and p53 by microdissection, polymerase chain reactions (PCR), nonradioisotopic single- strand conformation polymorphism (SSCP) analysis, and DNA sequencing. Each pulmonary lesion was microdissected from paraffin slides. Genomic DNA was amplified by two sequential PCRs followed by electrophoresis in a minigel and silver staining. Deoxyribonucleic acid sequencing was performed if necessary to confirm a mutation found upon SSCP analysis. Applying this molecular approach, we were able to differentiate the clonal origins of multiple malignant nodules of the lung as exemplified by the two cases presented.

Original languageEnglish (US)
Pages (from-to)179-184
Number of pages6
JournalDiagnostic Molecular Pathology
Volume6
Issue number4
DOIs
StatePublished - Aug 1997

Keywords

  • DNA sequencing
  • K-ras
  • Nonradioisotopic single-strand conformation polymorphism (SSCP)
  • P53
  • Polymerase chain reaction (PCR)
  • Synchronous lung cancers

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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