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A case of Turcot’s syndrome type 1 with loss of immunoexpression of MSH6 in colon cancer and liver metastasis due to secondary somatic mutation in coding mononucleotide (C)8 tract: a case report
- Source :
- BMC Medical Genetics, BMC Medical Genetics, Vol 21, Iss 1, Pp 1-7 (2020)
- Publication Year :
- 2020
- Publisher :
- BioMed Central, 2020.
-
Abstract
- Background Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes. Case presentation A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot’s syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis. Conclusion This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot’s syndrome type 1.
- Subjects :
- 0301 basic medicine
Male
Case Report
DNA Mismatch Repair
Metastasis
0302 clinical medicine
PMS2
Genetics (clinical)
Brain Neoplasms
Liver Neoplasms
Middle Aged
Lynch syndrome
Pedigree
DNA-Binding Proteins
medicine.anatomical_structure
Mismatch repair gene
030220 oncology & carcinogenesis
Colonic Neoplasms
Adenocarcinoma
Female
Colorectal Neoplasms
Adult
lcsh:Internal medicine
congenital, hereditary, and neonatal diseases and abnormalities
lcsh:QH426-470
MLH1
Descending colon
Frameshift mutation
03 medical and health sciences
Neoplastic Syndromes, Hereditary
Genetics
medicine
Humans
Genetic Predisposition to Disease
lcsh:RC31-1245
Turcot’s syndrome type 1
Base Sequence
business.industry
Somatic mutation
nutritional and metabolic diseases
Cancer
medicine.disease
digestive system diseases
lcsh:Genetics
030104 developmental biology
Mutation
Cancer research
Microsatellite instability
business
Microsatellite Repeats
Subjects
Details
- Language :
- English
- ISSN :
- 14712350
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- BMC Medical Genetics
- Accession number :
- edsair.doi.dedup.....338da9bc7b140d1695c5d7ac724c0369