||5R21CA209533-02 Interpret this number
||Sloan-Kettering Inst Can Research
||Candidate Gene Resequencing of Germline Multiple Myeloma
Myeloma accounts for almost 14% of all hematologic cancers and is essentially incurable.
Recent studies have documented increasing evidence for an inherited genetic basis for
multiple myeloma (MM). Genome-wide association studies have identified common variants
in transcriptional regulators and tumor suppressors associated with risk of sporadic MM and
we have recently identified presumed deleterious germline variants in a group of familial
cases following sequencing. As described in this application, we have already performed
exome sequencing of 934 probands and affected relatives. However, systematic analyses of
germline genetic alterations in sporadic and familial MM have not been performed to validate
the interesting candidate genes from these exome data. In this proposal, we will build on our
prior work and pre-existing genomic data to prioritize, identify and validate novel candidate
genes conferring susceptibility to MM. We also undertake a meta-analysis with an African
American study to understand commonality and heterogeneity of risks. These studies
represents the first systematic approach to understand the germline genetic variations in a
large group of well characterized MM cases and controls towards identification of moderate
and high risk genetic variants that predispose to MM, which will be of utility in prevention,
diagnosis, and modification of treatment of MM. Together, these studies will provide critical
new insights into the genetic basis of MM and lymphoid malignancies.
Sequencing at lymphoid neoplasm susceptibility loci maps six myeloma risk genes.
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