A

Endocrine-related cancer (2017-06-22)

Jan P Dumanski, Chiara Rasi, Peyman Björklund, Hanna Davies, Abir S Ali, Malin Grönberg, Staffan Welin, Halfdan Sorbye, Henning Grønbæk, Janet L Cunningham, Lars A Forsberg, Lars Lind, Erik Ingelsson, Peter Stålberg, Per Hellman, Eva Tiensuu Janson

PMID28634180

ABSTRACT

The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (