Elsevier

Seminars in Oncology

Volume 39, Issue 2, April 2012, Pages 125-131
Seminars in Oncology

Current clinical practice
Thirty-Nine-Year-Old With Familial Colon Cancer, and Variant of Undetermined Significance in MSH6

https://doi.org/10.1053/j.seminoncol.2012.01.013Get rights and content

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Case Study

A 39-year-old man presented with bone pain after a work-related injury. Imaging studies revealed several lesions throughout the spine that were suspicious for metastatic disease. Further workup, including a full-body computed tomography (CT) scan, showed a mass in the colon; this prompted a colonoscopy for a biopsy, which proved adenocarcinoma. The patient underwent resection of this lesion, and then was started on systemic chemotherapy for metastatic disease with FOLFOX (5-fluorouracil,

Clinical Genetics Experts' Opinion

The case report states that the MMR genes were tested by sequencing of the index case's DNA; in addition it should be verified that his DNA was also checked for any large deletions in the MMR genes by Southern blot analysis. Sequencing will tend to miss any of these deletions. If, in fact, the only genetic abnormalities to be found in this patient within the MMR genes are the two sequence variants in the MSH6 gene, then these variants should be checked for linkage within the pedigree. The DNA

Clinical Genetics Experts' Opinion

Genetic testing for cancer susceptibility offers the potential to clarify the cancer risks of patients and their relatives. A significant limitation of this process is the inconclusive result due to a VUS. Caution is warranted in interpreting a VUS result. In the setting of a patient or family who has chosen to pursue risk assessment and genetic testing to look for a suspected genetic risk, it can be tempting for both patient and clinician to assign causality to a VUS when a clearly deleterious

Clinical Genetics Experts' Opinion

The case presented demonstrates the importance of evaluating families for hereditary cancer syndromes, including the most common inherited colon cancer syndrome, called Lynch syndrome (also known as HNPCC). Genetic testing for genes known to cause Lynch syndrome is an important part of the evaluation process. In a small percentage of cases, sequence analysis of the genes associated with Lynch syndrome may identify genetic changes whose clinical significance is not yet known (usually missense

Conclusion

We present a case of a patient who has developed metastatic colorectal cancer at a young age, and who also has a strong family history of colorectal cancer, and ask how cancer risk can be managed in his family. His situation met criteria for genetic testing for Lynch syndrome (HNPCC); however, the MSH6 gene was found to have a deleterious mutation, a VUS further classified as a polymorphism or non-deleterious variant in the sequence. Commercial sequencing of MMR genes alone was done. Because

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