Microsatellite instability in keratoacanthoma.
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.
Halling
K C
KC
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Honchel
R
R
Pittelkow
M R
MR
Thibodeau
S N
SN
D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D004260:DNA Repair; D006801:Humans; D007636:Keratoacanthoma / Q000235:genetics*; D009074:Melanocyte-Stimulating Hormones / Q000235:genetics; D018895:Microsatellite Repeats; D008875:Middle Aged; D008969:Molecular Sequence Data
D009074:Melanocyte-Stimulating Hormones