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PMID: 7937908 Published · ppublish English Clinical Trial Controlled Clinical Trial Journal Article Research Support, U.S. Gov't, P.H.S.

Microsatellite alterations as clonal markers for the detection of human cancer.

Mao L, Lee DJ, Tockman MS, Erozan YS, Askin F, Sidransky D

Abstract

Microsatellite instability has been reported to be an important feature of tumors from hereditary nonpolyposis colorectal carcinoma (HNPCC) patients. The recent discovery of genetic instability in small cell lung carcinoma, a neoplasm not associated with HNPCC, led us to investigate the possible presence of microsatellite alterations in other tumor types. We examined 52 microsatellite repeat sequences in the DNA of normal and tumor pairs from 100 head and neck, bladder, and lung cancer patients by the polymerase chain reaction. Although alterations were rare in dinucleotide repeats, larger (tri- or tetranucleotide) repeats were found to be more prone to expansion or deletion. We screened 100 tumors with a panel of nine tri- and tetranucleotide repeat markers and identified 26 (26%) that displayed alterations in at least one locus. This observation prompted us to examine the possibility of using microsatellite alterations as markers to detect clonal tumor-derived cell populations in pathologic samples. The identical microsatellite alterations detected in the primary tumors were successfully identified in corresponding urine, sputum, and surgical margins from affected patients. This study demonstrates that appropriately selected microsatellite loci are commonly altered in many cancers and can serve as clonal markers for their detection.

MeSH Terms
Base Sequence Biomarkers, Tumor/analysis Carcinoma, Non-Small-Cell Lung/genetics,pathology Carcinoma, Small Cell/genetics,pathology Colorectal Neoplasms, Hereditary Nonpolyposis/genetics,pathology DNA Primers DNA, Neoplasm/analysis,genetics DNA, Satellite/analysis,genetics Head and Neck Neoplasms/genetics,pathology Humans Lung Neoplasms/genetics,pathology Molecular Sequence Data Neoplasms/genetics,pathology Polymerase Chain Reaction Reference Values Repetitive Sequences, Nucleic Acid Urinary Bladder Neoplasms/genetics,pathology
Chemicals
Biomarkers, Tumor DNA Primers DNA, Neoplasm DNA, Satellite
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Mao L
Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196.
Lee D J
Tockman M S
Erozan Y S
Askin F
Sidransky D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1994-10-11
Pages
9871-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44919
Subset
IM
Grants
NCI NIH HHS · CA-58184-01 · United States
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