Constitutional Mismatch Repair-Deficiency Syndrome Is a Rare Cause of Cancer Even in a Highly Consanguineous Population — Oak Academic Publishing
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Constitutional Mismatch Repair-Deficiency Syndrome Is a Rare Cause of Cancer Even in a Highly Consanguineous Population
Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Cancer, Riyadh, Saudi Arabia
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Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Cancer, Riyadh, Saudi Arabia
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Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Cancer, Riyadh, Saudi Arabia
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Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 3De- partment of Pathology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Cancer, Riyadh, Saudi Arabia
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Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
1 Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Cancer, Riyadh, Saudi Arabia
2 Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Cancer, Riyadh, Saudi Arabia
3 Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Cancer, Riyadh, Saudi Arabia
4 Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 3De- partment of Pathology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
5 Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Cancer, Riyadh, Saudi Arabia
6 Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Biallelic germline mutations in the mismatch repair genes, including MLH 1, MSH 2, MSH 6 or PMS 2, lead to a recess ive constitutional mismatch repair-deficiency (CMMR-D) syndrome characterized by early onset malignancies in chil dren and young adults. Because consanguinity unmasks autosomal recessive disorders, we hypothesized that the fre quency of CMMR-D is inflated in the highly consanguineous population of Saudi Arabia. In this study, 371 pediatric and young adult patient samples from Saudi Arabia that cover the tumor spectrum of CMMR-D syndrome were ana lyzed for biallelic germline mutations in the MLH 1, MSH 2, MSH 6 and PMS 2 with the use of direct genomic sequencing. However, none of the 371 patients involved in the study was found to have biallelic pathological mutations of MLH 1, MSH 2, MSH 6 or PMS 2. This result indicates that CMMR-D is exceptionally rare among pediatric cancer patients and adult early onset cancer patients, even in the highly consanguineous Saudi population. Our findings suggest that larger cohorts will be needed, particularly in outbred populations, to determine the frequency of CMMR-D and that routine screening for this syndrome among cancer patients is not warranted.
KeywordsConstitutional Mismatch Repair-Deficiency (CMMR-D)Lynch Syndrome (LS)MLH1MSH2MSH6 and PMS2Biallelic Germline Mutations
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