Identification of a novel MSH6 germline variant in a family with multiple gastro-intestinal malignancies by next generation sequencing.
The identification of germline variants that predispose to cancer is important to further our understanding of tumorigenesis, guide patient management, prevent disease in unaffected relatives, and inform best practice for health care. We describe a kindred with multiple gastrointestinal malignancies where a novel MSH6 germline susceptibility variant was identified by exome sequencing after eluding serial routine testing in multiple affected members. This case fosters discussion of our current understanding of DNA mismatch repair deficiency, the management of Lynch Syndrome, and the emerging role of next generation sequencing in laboratory medicine to identify rare pathogenic germline variants in a comprehensive, unbiased fashion.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada, ashton.connor@utoronto.ca.
Ashton A
AA
Connor
Hagit
H
Katzov-Eckert
Thomas
T
Whelan
Melyssa
M
Aronson
Lynette
L
Lau
Christian
C
Marshall
George S
GS
Charames
Aaron
A
Pollett
Steven
S
Gallinger
Jordan
J
Lerner-Ellis
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010375:Pedigree
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein