Microsatellite instability in keratoacanthoma

K. C. Halling, R. Honchel, M. R. Pittelkow, Stephen N Thibodeau

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background. Tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and from a subset of patients with the related Muir-Torre syndrome (MTS) exhibit a novel type of genomic instability known as microsatellite instability (MIN). In general, this form of genomic instability results from mutations that inactivate DNA mismatch repair genes. The detection of MIN in a keratoacanthoma (KA) from a patient with MTS suggested that defective mismatch repair may play a role in the pathogenesis of these neoplasms. Methods. Randomly selected paraffin embedded KA from 53 patients and paraffin embedded tumors from an additional 12 patients diagnosed with KA and colorectal carcinoma were examined for MIN at six loci. In addition, several KA were examined for mutations within the hMSH2 gene. Results. Six of the 53 randomly selected KAs had MIN at two or more loci. One of these six patients had HNPCC, whereas another had MTS. Two patients with KAs lacking MIN had colon tumors that exhibited widespread MIN, and one of these patients had MTS. Three of the 12 additional patients diagnosed with a KA and a colorectal carcinoma had at least one tumor that had MIN at two or more loci, and one of these patients had HNPCC. A 2-base pair somatic deletion in exon 3 of the hMSH2 gene was identified in one of the MIN+KAs. Conclusions. Defective mismatch repair appears to play a role in the process of tumorigenesis in some KAs. Microsatellite instability in a KA or the cooccurrence of a colorectal carcinoma and a KA in a patient suggests that the patient may have either HNPCC or its phenotypic variant MTS.

Original languageEnglish (US)
Pages (from-to)1765-1771
Number of pages7
JournalCancer
Volume76
Issue number10
DOIs
StatePublished - 1995

Fingerprint

Keratoacanthoma
Microsatellite Instability
Muir-Torre Syndrome
Hereditary Nonpolyposis Colorectal Neoplasms
DNA Mismatch Repair
Colorectal Neoplasms
Genomic Instability
Neoplasms
Paraffin
Genes
Mutation
Base Pairing
Exons

Keywords

  • DNA mismatch repair
  • hereditary nonpolyposis colorectal cancer
  • keratoacanthoma
  • microsatellite instability
  • Muir-Torre syndrome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Microsatellite instability in keratoacanthoma. / Halling, K. C.; Honchel, R.; Pittelkow, M. R.; Thibodeau, Stephen N.

In: Cancer, Vol. 76, No. 10, 1995, p. 1765-1771.

Research output: Contribution to journalArticle

Halling, K. C. ; Honchel, R. ; Pittelkow, M. R. ; Thibodeau, Stephen N. / Microsatellite instability in keratoacanthoma. In: Cancer. 1995 ; Vol. 76, No. 10. pp. 1765-1771.
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abstract = "Background. Tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and from a subset of patients with the related Muir-Torre syndrome (MTS) exhibit a novel type of genomic instability known as microsatellite instability (MIN). In general, this form of genomic instability results from mutations that inactivate DNA mismatch repair genes. The detection of MIN in a keratoacanthoma (KA) from a patient with MTS suggested that defective mismatch repair may play a role in the pathogenesis of these neoplasms. Methods. Randomly selected paraffin embedded KA from 53 patients and paraffin embedded tumors from an additional 12 patients diagnosed with KA and colorectal carcinoma were examined for MIN at six loci. In addition, several KA were examined for mutations within the hMSH2 gene. Results. Six of the 53 randomly selected KAs had MIN at two or more loci. One of these six patients had HNPCC, whereas another had MTS. Two patients with KAs lacking MIN had colon tumors that exhibited widespread MIN, and one of these patients had MTS. Three of the 12 additional patients diagnosed with a KA and a colorectal carcinoma had at least one tumor that had MIN at two or more loci, and one of these patients had HNPCC. A 2-base pair somatic deletion in exon 3 of the hMSH2 gene was identified in one of the MIN+KAs. Conclusions. Defective mismatch repair appears to play a role in the process of tumorigenesis in some KAs. Microsatellite instability in a KA or the cooccurrence of a colorectal carcinoma and a KA in a patient suggests that the patient may have either HNPCC or its phenotypic variant MTS.",
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N2 - Background. Tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and from a subset of patients with the related Muir-Torre syndrome (MTS) exhibit a novel type of genomic instability known as microsatellite instability (MIN). In general, this form of genomic instability results from mutations that inactivate DNA mismatch repair genes. The detection of MIN in a keratoacanthoma (KA) from a patient with MTS suggested that defective mismatch repair may play a role in the pathogenesis of these neoplasms. Methods. Randomly selected paraffin embedded KA from 53 patients and paraffin embedded tumors from an additional 12 patients diagnosed with KA and colorectal carcinoma were examined for MIN at six loci. In addition, several KA were examined for mutations within the hMSH2 gene. Results. Six of the 53 randomly selected KAs had MIN at two or more loci. One of these six patients had HNPCC, whereas another had MTS. Two patients with KAs lacking MIN had colon tumors that exhibited widespread MIN, and one of these patients had MTS. Three of the 12 additional patients diagnosed with a KA and a colorectal carcinoma had at least one tumor that had MIN at two or more loci, and one of these patients had HNPCC. A 2-base pair somatic deletion in exon 3 of the hMSH2 gene was identified in one of the MIN+KAs. Conclusions. Defective mismatch repair appears to play a role in the process of tumorigenesis in some KAs. Microsatellite instability in a KA or the cooccurrence of a colorectal carcinoma and a KA in a patient suggests that the patient may have either HNPCC or its phenotypic variant MTS.

AB - Background. Tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and from a subset of patients with the related Muir-Torre syndrome (MTS) exhibit a novel type of genomic instability known as microsatellite instability (MIN). In general, this form of genomic instability results from mutations that inactivate DNA mismatch repair genes. The detection of MIN in a keratoacanthoma (KA) from a patient with MTS suggested that defective mismatch repair may play a role in the pathogenesis of these neoplasms. Methods. Randomly selected paraffin embedded KA from 53 patients and paraffin embedded tumors from an additional 12 patients diagnosed with KA and colorectal carcinoma were examined for MIN at six loci. In addition, several KA were examined for mutations within the hMSH2 gene. Results. Six of the 53 randomly selected KAs had MIN at two or more loci. One of these six patients had HNPCC, whereas another had MTS. Two patients with KAs lacking MIN had colon tumors that exhibited widespread MIN, and one of these patients had MTS. Three of the 12 additional patients diagnosed with a KA and a colorectal carcinoma had at least one tumor that had MIN at two or more loci, and one of these patients had HNPCC. A 2-base pair somatic deletion in exon 3 of the hMSH2 gene was identified in one of the MIN+KAs. Conclusions. Defective mismatch repair appears to play a role in the process of tumorigenesis in some KAs. Microsatellite instability in a KA or the cooccurrence of a colorectal carcinoma and a KA in a patient suggests that the patient may have either HNPCC or its phenotypic variant MTS.

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