Date of Graduation
5-2018
Document Type
Thesis (MS)
Program Affiliation
Genetic Counseling
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Leslie Dunnington
Committee Member
Michelle Jackson
Committee Member
Krista Qualmann
Committee Member
Syed Hashmi
Committee Member
Aarti Ramdaney
Committee Member
David Rodriguez-Buritica
Abstract
Background. Currently, there are no genetic testing guidelines for patients with a primary brain tumor (PBT). This population is largely understudied in terms of the family history, tumor grade, pathology, and their relation to genetic contribution. Our aim was to describe patient-specific characteristics and family histories across mutation-positive, negative, and variant of uncertain significance (VUS) cohorts based on cancer-panel genetic test results among patients with a PBT.
Methods. Subjects were referred for multi-gene panel testing between March 2012 and June 2016. Clinical data were ascertained from test requisition forms. The incidence of pathogenic mutations (including likely pathogenic) and VUS’s were calculated for each gene and patient cohort.
Results. Almost all tumors were glial (n=293, 53%) or meningeal pathology (n=222, 40%). Age of diagnosis differed significantly between glial and meningeal tumors (pCHEK2 (20/104), BRCA2 (13/104), PMS2 (10/104), TP53 (8/104), and APC (8/104). Of 165 patients with available family history information, nearly all (n=157, 95%) reported a family history of some cancer.
Conclusions. Our data suggest PBTs can be the primary presenting cancer in hereditary syndromes with a known PBT risk. While pathology is helpful in narrowing down the differential diagnosis, patients’ pathology can be atypical in relation to their hereditary cancer syndrome. Family history evaluations are a beneficial risk assessment modality, particularly until testing criteria are developed for PBTs. Further research is necessary for the development of genetic testing criteria in the PBT population and more robust identification of at-risk individuals.
Keywords
Primary brain tumors, Genetics, Genetic testing, Panel testing, Hereditary cancer