High frequency of clonally related tumors in cases of multiple synchronouslung cancers as revealed by molecular diagnosis

Citation
S. Shimizu et al., High frequency of clonally related tumors in cases of multiple synchronouslung cancers as revealed by molecular diagnosis, CLIN CANC R, 6(10), 2000, pp. 3994-3999
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
6
Issue
10
Year of publication
2000
Pages
3994 - 3999
Database
ISI
SICI code
1078-0432(200010)6:10<3994:HFOCRT>2.0.ZU;2-7
Abstract
In patients with multiple synchronous lung tumors, discrimination of multic entric lung cancers from intrapulmonary metastasis is important for treatme nt decision, but this is sometines difficult. The aim of this study was to retrospectively distinguish multicentric lung cancers from intrapulmonary m etastases in 14 such cases by loss of heterozygosity (LOH) and p53 mutation al status. DNA was extracted from microdissected tumor cells in paraffin-em bedded archival tissue, and 3p14.2, 3p21, 3p25, 9p21, and 18q21.1 were inve stigated for LOH. Exons 5-8 of the p53 gene were examined for mutations by the PCR, followed by single-strand conformation polymorphism analysis and D NA sequencing. For cases with the same LOH pattern, we calculated a clonali ty index, the probability of the given LOH pattern when these tumors were h ypothesized to be independent in origin, Eleven of 14 cases (79%) were thus diagnosed as having pulmonary metastasis and only one case as having genui nely multicentric lung cancers. Two cases presented difficulty in diagnosis . In several cases, the LOH patterns conflicted with p53 mutation patterns, suggesting that clonal evolution is directly affected by certain genetic c hanges. The combination of p53 with LOH helped increase both the sensitivit y and specificity of the assay.