Research Papers:

Fanconi Anemia germline variants as susceptibility factors in aplastic anemia, MDS and AML

Bartlomiej Przychodzen _, Hideki Makishima, Mikkael A. Sekeres, Suresh Kumar Balasubramanian, Swapna Thota, Bhumika J. Patel, Michael Clemente, Cassandra Hirsch, Brittney Dienes and Jaroslaw P. Maciejewski

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Oncotarget. 2018; 9:2050-2057. https://doi.org/10.18632/oncotarget.23328

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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

Correspondence to:

Bartlomiej Przychodzen, email: [email protected]

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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