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Microsatellite instability in keratoacanthoma
K C Halling1, R Honchel, M R Pittelkow
1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
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.
Insights
Microsatellite instability (MIN), a sign of defective DNA repair, is found in some keratoacanthomas (KAs). This suggests a link between MIN in KAs and hereditary nonpolyposis colorectal cancer (HNPCC) or Muir-Torre syndrome (MTS).
Area of Science:
- Oncology
- Genetics
- Dermatology
Background:
- Hereditary nonpolyposis colorectal cancer (HNPCC) and Muir-Torre syndrome (MTS) are associated with microsatellite instability (MIN).
- MIN results from mutations inactivating DNA mismatch repair genes.
- Defective DNA mismatch repair is implicated in the pathogenesis of keratoacanthomas (KAs) in MTS patients.
Purpose of the Study:
- To investigate the presence of MIN in keratoacanthomas (KAs).
- To explore the association between MIN in KAs and hereditary nonpolyposis colorectal cancer (HNPCC) or Muir-Torre syndrome (MTS).
Main Methods:
- Examined 53 randomly selected KAs and 12 additional KAs with colorectal carcinoma for MIN at six loci.
- Analyzed KAs for mutations in the hMSH2 gene.
Main Results:
- Six of 53 KAs exhibited MIN at two or more loci; one patient had HNPCC, another had MTS.
- Two KAs without MIN were from patients with colon tumors showing widespread MIN, one with MTS.
- A 2-base pair deletion in the hMSH2 gene was identified in one MIN-positive KA.
Conclusions:
- Defective DNA mismatch repair contributes to tumorigenesis in a subset of KAs.
- The presence of MIN in KAs or co-occurrence with colorectal carcinoma suggests potential HNPCC or MTS.