Danielle Connacher
Danielle Connacher
Helios Scholar
School: University of Arizona
Hometown: Tempe, Arizona
Mentor:Tyler Izatt
PI: Sara Byron, PhD 

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Examining health disparities through germline structural variant analysis

Disparities exist in cancer onset and outcomes within the Hispanic population in the United States, with several studies reporting a younger age of onset for certain cancer types. Within a City of Hope Pan-Cancer Cohort (n=1218), Hispanic patients were diagnosed with cancer an average of ~10 years earlier than non-Hispanic patients. Although prior research indicates pathogenic germline single nucleotide variants do not account for this discrepancy, the incidence of pathogenic germline structural variants (PGSVs) within this cohort has not been explored. To determine the prevalence of PGSVs, germline structural variations were called from constitutional whole exome sequencing data using Manta, and the pathogenicity of the structural variations was annotated using the program AnnotSV. Results were filtered to isolate PGSVs on cancer-linked genes. PGSVs were identified in 0.25% (3/1218) of cancer patients, including a BRCA1 exon 13 duplication event in a young patient with ovarian cancer. This event was previously reported by clinical genetic testing, validating our approach. Two previously unidentified PGSVs were found: a duplication on BRCA2 seen in a bladder cancer patient, and a deletion in MFSD3 and RECQL4 seen in a young patient with breast cancer. These findings support AnnotSV’s value in identifying patients with PGSVs. PGSVs of cancer-linked genes may contribute to the younger age of diagnosis in a small subset of patients, but alone does not account for the age disparity observed within the Hispanic portion of this cohort. Further studies are needed to explore other factors contributing to this cancer health disparity.