Fanconi Anemia germline variants as susceptibility factors in aplastic anemia, MDS and AML
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Bartlomiej Przychodzen1, Hideki Makishima1, Mikkael A. Sekeres1, Suresh Kumar Balasubramanian1, Swapna Thota1, Bhumika J. Patel1, Michael Clemente1, Cassandra Hirsch1, Brittney Dienes1 and Jaroslaw P. Maciejewski1
1Department of Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Bartlomiej Przychodzen, email: email@example.com
Keywords: Fanconi Anemia; MDS; AML; germline
Received: February 07, 2017 Accepted: December 08, 2017 Published: December 16, 2017
Using next generation sequencing we have systematically analyzed a large cohort of 489 patients with bone marrow failure (BMF), including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), aplastic anemia (AA), and related conditions for the presence of germline (GL) alterations in Fanconi Anemia (FA) and telomerase genes. We have detected an increased frequency of heterozygous FA gene mutations in MDS and to lesser degree in AML suggesting that the presence of one normal allele may not be completely protective and indeed heterozygous FA lesions may have a long latency period before hematologic manifestation. In contrast, GL telomerase gene mutations were not associated with increased disease risk. When compared to large control cohorts, we have not detected an increased frequency of damaging variants among telomerase complex genes, including those previously believed to be involved in the pathogenesis of AA. Our results may suggest that while low penetrance and delayed disease onset can confound identification of genetic predisposition factors, GL FA alterations can be also associated with MDS.
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