Tumor necrosis factor-α allelic frequency and chromosome 6 allelic imbalance in patients with colorectal cancer

Ronald Honchel, Shannon McDonnell, Daniel J Schaid, Stephen N Thibodeau

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The human tumor necrosis factor (TNF) locus is located on chromosome 6p21.3 and contains at least five polymorphic microsatellites. In this study, we compared the allelic frequencies derived from 50 normal controls to 64 patients with colorectal cancer at one of these loci, TNFα. No differences in allelic frequencies were observed between these two groups (P = 0.47). However, sequencing of the TNFα PCR product revealed two populations of TNFα alleles; alleles with the expected DNA sequence (i.e., the expected number of AC/GT repeats) and alleles that contained 8-bp deletions adjacent to the microsatellite repeat. In addition, we also examined paired normal and tumor DNA from the colorectal cancer group for microsatellite alterations at the TNFα, locus, including allelic loss of heterozygosity and microsatellite instability. Of the 64 tumors examined, 13 (20%) demonstrated microsatellite instability, and 14 (42%) of 33 informative cases demonstrated allelic imbalance. Analysis of 10 additional chromosome 6 loci for allelic loss showed that 23 (47%) of 49 informative cases exhibited allelic imbalance with at least one chromosome 6p marker, 23 (47%) of 49 with at least one 6q marker, and 29 (59%) of 49 with at least one marker on chromosome 6. Examination of tumors for the minimal region of deletion overlap suggests the presence of tumor suppressor genes on both 6p and 6q.

Original languageEnglish (US)
Pages (from-to)145-149
Number of pages5
JournalCancer Research
Volume56
Issue number1
StatePublished - Jan 1 1996

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Allelic Imbalance
Chromosomes, Human, Pair 6
Loss of Heterozygosity
Colorectal Neoplasms
Tumor Necrosis Factor-alpha
Microsatellite Repeats
Microsatellite Instability
Alleles
Neoplasms
Tumor Suppressor Genes
Genetic Markers
Chromosomes
Polymerase Chain Reaction
DNA
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tumor necrosis factor-α allelic frequency and chromosome 6 allelic imbalance in patients with colorectal cancer. / Honchel, Ronald; McDonnell, Shannon; Schaid, Daniel J; Thibodeau, Stephen N.

In: Cancer Research, Vol. 56, No. 1, 01.01.1996, p. 145-149.

Research output: Contribution to journalArticle

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abstract = "The human tumor necrosis factor (TNF) locus is located on chromosome 6p21.3 and contains at least five polymorphic microsatellites. In this study, we compared the allelic frequencies derived from 50 normal controls to 64 patients with colorectal cancer at one of these loci, TNFα. No differences in allelic frequencies were observed between these two groups (P = 0.47). However, sequencing of the TNFα PCR product revealed two populations of TNFα alleles; alleles with the expected DNA sequence (i.e., the expected number of AC/GT repeats) and alleles that contained 8-bp deletions adjacent to the microsatellite repeat. In addition, we also examined paired normal and tumor DNA from the colorectal cancer group for microsatellite alterations at the TNFα, locus, including allelic loss of heterozygosity and microsatellite instability. Of the 64 tumors examined, 13 (20{\%}) demonstrated microsatellite instability, and 14 (42{\%}) of 33 informative cases demonstrated allelic imbalance. Analysis of 10 additional chromosome 6 loci for allelic loss showed that 23 (47{\%}) of 49 informative cases exhibited allelic imbalance with at least one chromosome 6p marker, 23 (47{\%}) of 49 with at least one 6q marker, and 29 (59{\%}) of 49 with at least one marker on chromosome 6. Examination of tumors for the minimal region of deletion overlap suggests the presence of tumor suppressor genes on both 6p and 6q.",
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