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Introduction Although multiple predispositions to hematologic malignancies exist, evaluations for hereditary cancer syndromes (HCS) are underperformed by most hematologist/oncologists. Criteria for initiating HCS evaluation are poorly defined, and results of genetic testing for hereditary hematologic malignancies have not been systematically reported. Patients and Methods From April 2014 to August 2015, 67 patients were referred to the Hereditary Hematologic Malignancy Clinic (HHMC). Referral reasons included (1) bone marrow failure or myelodysplastic syndrome in patients ≤ 50 years, (2) evaluation for germ-line inheritance of identified RUNX1 , GATA2 , or CEBPA mutations on targeted next-generation sequencing panels, and (3) strong personal and/or family history of malignancy. Cultured skin fibroblasts were utilized for germ-line DNA in all patients with hematologic malignancy. Results Eight patients (12%) were clinically diagnosed with a HCS: 4 patients with RUNX1 -related familial platelet disorder (FPD)/acute myeloid leukemia (AML), and 1 patient each with dyskeratosis congenita, Fanconi anemia, germ-line DDX41 , and Li-Fraumeni syndrome (LFS). Two patients with concern for FPD/AML and LFS, respectively, had RUNX1 and TP53 variants of unknown significance. Additionally, 4 patients with prior HCS diagnosis (1 LFS, 3 FPD/AML) were referred for further evaluation and surveillance. Conclusion In this HHMC-referred hematologic malignancy cohort, HCS was confirmed in 12 patients (18%). HCS identification provides insight for improved and individualized treatment, as well as screening/surveillance opportunities for family members. The HHMC has facilitated HCS diagnosis; with increased clinical awareness of hematologic malignancy predisposition syndromes, more patients who may benefit from evaluation can be identified. Mutation panels intended for prognostication may provide increased clinical suspicion for germ-line testing.

5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) play a critical role in development and normal physiology. Alterations in 5-mC and 5-hmC patterns are common events in hematopoietic neoplasms. In this review, we begin by emphasizing the importance of 5-mC, 5-hmC, and their enzymatic modifiers in hematological malignancies. Then, we discuss the functions of 5-mC and 5-hmC at distinct genic contexts, including promoter regions, gene bodies, intron-exon boundaries, alternative promoters, and intragenic microRNAs. Recent advances in technology have allowed for the study of 5-mC and 5-hmC independently and specifically permitting distinction between the bases that show them to have transcriptional effects that vary by their location relative to gene structure. We extend these observations to their functions at enhancers and transcription factor binding sites. We discuss dietary influences on 5-mC and 5-hmC levels and summarize the literature on the effects of folate and vitamin C on 5-mC and 5-hmC, respectively. Finally, we discuss how these new themes in the functions of 5-mC and 5-hmC will likely influence the broader research field of epigenetics.