Abstract 1923: Constitutional mismatch repair-deficiency syndrome is a rare cause of cancer even in a highly consanguineous population.

Abstract

Abstract Background: Biallelic germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2 cause a recessive childhood cancer syndrome characterized by early onset malignancies and signs reminiscent of neurofibromatosis type 1 (NF1). This syndrome is known as constitutional mismatch repair-deficiency (CMMR-D) syndrome. Because consanguinity unmasks autosomal recessive disorders, we hypothesized that the frequency of CMMR-D is inflated in the highly consanguineous population of Saudi Arabia. Methods: 372 patient samples from Saudi Arabia that cover the tumor spectrum of CMMR-D syndrome were analyzed for biallelic germline mutations in the MLH1, MSH2, MSH6 and PMS2 with the use of direct genomic sequencing. Results: None of the 372 patients involved in the study was found to have biallelic pathological mutations of MLH1, MSH2, MSH6 or PMS2. Conclusion: 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. Citation Format: Rong Bu, Abdul K. Siraj, Prashant Bavi, Asim Belgaumi, Wael Al-Haqawi, Fouad Al-Dayel, Shahab Uddin, Fowzan S. Alkuraya, Khawla S. Al-Kuraya. Constitutional mismatch repair-deficiency syndrome is a rare cause of cancer even in a highly consanguineous population. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1923. doi:10.1158/1538-7445.AM2013-1923