Inter- and intra-individual variability in somatic allele loss in ductal carcinoma of the breast

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133564

Rebbeck, T; Godwin, A; Rosvold, E ^[1]

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1. Fox Chase Cancer Center, Philadelphia, PA (United States); and others

The etiology of most cancers involves both inherited genetic susceptibility and somatic genetic changes. We studied 28 ductal carcinomas of the breast to evaluate variability in loss of constitutional heterozygosity (LOH) across loci and across individuals and to assess the relationship of candidate genes with LOH. LOH was measured on 33 chromosome arms using the most telomeric, highly heterozygous tetranucleotide repeat markers from the Cooperative Human Linkage Center (CHLC). The overall mean proportion of LOH was 11%. The proportion of LOH ranged from 0% to 37% across loci. LOH > 20% was observed at chromosomes 1p, 7q, 10q, 11p, 17p, and 18q. Of these, simultaneous losses at the following locus pairs occurred more often than expected: 1p & 11p; 1p & 17p; 7q & 18q; 11p & 17p. An elevated proportion of LOH was not observed for the marker on chromosome 17q. The proportion of LOH ranged from 0% to 67% across individuals. 20 tumors showed less than 10% LOH, and 6 showed more than 20% LOH. There was no correlation between LOH and tumor stage. To examine whether variability in candidate genes was associated with LOH, allelic variability was measured at CYP1A1, CYP2D6, epoxide hydrolase (EH), HADP(H):quinone oxidoreductase (NQO1), and glutathione-S-transferase-{mu} (GST-{mu}). An elevated proportion of LOH was observed for genotypes at CYP2D6 (17% for 1/1, 1/2`s vs. 8% for 2/2`s), NQO1 (13% for 1/2, 2/2`s vs. 8% for 1/1`s), and GST-{mu} (15% for {open_quotes}null{close_quotes} genotypes vs. 7% for wild types), but not at CYP1A1 (12% for 1/2`s vs. 10% for 1/1`s) or EH (11% for 1/1`s vs. 10% for 1/2`s). Our results suggest that LOH is not randomly distributed across the genome, and that there is substantial interindividual variability in LOH. This interindividual variability may be explained by genes that metabolize environmental carcinogens or steroid hormones.

• OSTI ID: 133564
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
CARCINOMAS
CHROMOSOMAL ABERRATIONS
ETIOLOGY
GENES
GENETIC MAPPING
GENETIC VARIABILITY
GENOTYPE
HUMAN CHROMOSOMES
MAMMARY GLANDS
PATIENTS
SOMATIC MUTATIONS
STATISTICS