Volume 1, Issue 3 pp. 240-246
Research Article
Full Access

Molecular mapping of deletion sites in the short arm of chromosome 3 in human lung cancer

Dr. Hiltrud Brauch

Corresponding Author

Dr. Hiltrud Brauch

Laboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland

Cellular Immunity Section, Laboratory of Immunobiology, Bldg. 560, Rm. 12–34, National Cancer Institute, Frederick Cancer Research Facility, Frederick, MD 21701Search for more papers by this author
Kalman Tory

Kalman Tory

Laboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland

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Frederick Kotler

Frederick Kotler

Laboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland

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Adi F. Gazdar

Adi F. Gazdar

NCI, Navy Medical Oncology Branch, Naval Hospital, Bethesda, Maryland

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Olive S. Pettengill

Olive S. Pettengill

Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire

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Bruce Johnson

Bruce Johnson

NCI, Navy Medical Oncology Branch, Naval Hospital, Bethesda, Maryland

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Stephen Graziano

Stephen Graziano

Department of Medicine, SUNY Health Science Center and Veterans Administration Medical Center, Syracuse, New York

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Tim Winton

Tim Winton

NCI, Navy Medical Oncology Branch, Naval Hospital, Bethesda, Maryland

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Charles H. C. M. Buys

Charles H. C. M. Buys

Department of Human Genetics, State University of Groningen, Groningen, The Netherlands

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George D. Sorenson

George D. Sorenson

Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire

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Bernard J. Poiesz

Bernard J. Poiesz

Department of Medicine, SUNY Health Science Center and Veterans Administration Medical Center, Syracuse, New York

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John D. Minna

John D. Minna

NCI, Navy Medical Oncology Branch, Naval Hospital, Bethesda, Maryland

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Berton Zbar

Berton Zbar

Laboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland

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First published: January 1990
Citations: 67

Abstract

We used 10 restriction fragment length polymorphism (RFLP) probes spanning the length of the short arm of chromosome 3 (3p) to map deletion sites in human lung cancer. Two approaches were used. 1) When a patient's tumor and normal tissue were available, loci with allelic heterozygosity in the normal tissue were tested for loss of alleles at 3p. 2) When the corresponding normal tissue was not available, the frequency of heterozygosity at each locus in a panel of tumors was compared to the corresponding published frequencies in nontumor tissue of healthy individuals or patients with lung cancer. In 14 small cell lung carcinomas (SCLC) with normal DNA for comparison, allele loss was found at all heterozygous loci, with one exception at a locus near the 3p centromere (D3S4). In the total of 53 SCLCs, which included tumors without paired normal tissue, frequency of heterozygosity was significantly reduced in all 10 3p loci. Three loci, DNF15S2, RAF1, and D3S18, were homozygous in all tumors in the SCLC panel. These loci, which are in regions 3p21 and 3p25, may thus be involved in the origin or evolution of SCLC. We also investigated 24 non-SCLC tumors. In this panel, frequency of heterozygosity was significantly reduced at seven of the 10 loci tested. Comparison of the results shows that the pattern of allele loss on 3p is different in SCLC and non-SCLC, suggesting a difference in pathogenesis at the genetic level.

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