UNIVERSAL GENETIC TESTING OF PATIENTS WITH HEMATOLOGICAL MALIGNANCIES (UGT)

Genetic data is transforming the understanding and management of cancers of all types.

The detection of pathogenic germline genetic variants (mutations) underlying the formation of cancer is important because the genetic information can inform optimal treatment for individuals with cancer and can be used to modify cancer risk in family members who are carriers for the variant but who have not developed cancer. Germline next generation sequencing (NGS) has only recently begun to be used to assess for hereditary risk in hematological malignancies (HM), and in particular beyond myeloid HMs. NGS detects small genetics changes such single base substitutions and small deletions, whereas a new technique called optical genome mapping (OGM) is able to detect large structural genetic changes in tumor DNA. OGM is well established here in Molecular Pathology but has only recently been applied to the study of HMs.

We propose to perform NGS and OGM with DNA extracted from bone marrow (BM; site of cancer) and NGS on skin fibroblast DNA (proxy for germline) on all patients with hematologic malignancies (HM) who undergo a standard-of-care BM biopsy at Georgia Cancer Center/Wellstar MCG Health. Simultaneous 4 mm punch skin biopsy for fibroblast culture will be obtained at the planned puncture site of the BM biopsy. The bone marrow biopsy and aspirate are already part of the patient's scheduled medical evaluation and the punch biopsy of the skin is the only additional procedure involved in the study. We will compare BM and germline variants in order to determine their rate and concordance, examine the percent of germline variants that are likely to be the cause of the HM, assess the impact of the germline finding on treatment choices, and determine the impact of germline findings on family members. New data from OGM will be compared to NGS