Somatic allele loss in genetic linkage analysis of cancer

Timothy R. Rebbeck, Edward D. Lustbader, Kenneth H. Buetow

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The ability to detect or reject genetic linkage in studies of human cancer is often diminished because multiple affected relatives in a pedigree are unavailable for analysis. The observation of somatic allele loss in tumors can provide knowledge about gametic phase. Therefore, consideration of tumor genotype data could be used to obtain knowledge about gametic phase ordinarily gained from a larger sample of individuals in cancer families. The objective of the present study is to describe a method for improving the power to detect or reject genetic linkage by using knowledge about somatic genetic changes in tumor tissue. A modification to the lod score method of linkage analysis is proposed in which knowledge of gametic phase in the linkage likelihood is inferred from observations of loss of constitutional heterozygosity (LoH) in tumor tissue. This methodology was evaluated using a double backcross nuclear family with a pair of offspring. The expected lod score improved substantially when tumor genotype data were included in the analysis. For example, when the haplotype remaining in tumor tissue was identical to the inherited haplotype in constitutional tissue 99% of the time, linkage analyses without tumor genotype data would require a 2–5 times larger sample of offspring pairs to conclude linkage with an expected lod score value of 3 or greater, compared to analyses incorporating tumor genotype data. These results suggest that consideration of tumor genotype data using the proposed method can substantially improve the power of linkage analyses in cancer families. © 1994 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)419-429
Number of pages11
JournalGenetic Epidemiology
Volume11
Issue number5
DOIs
StatePublished - 1994

Keywords

  • family cancer syndromes
  • lod score
  • loss of heterozygosity
  • somatic genetic mutation
  • tumor suppressor genes

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

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