Mutations in the ATM gene have been identified as
a predisposition gene for pancreatic ductal adenocarcinoma, according to data
published online in Cancer Discovery, a journal of the American
Association for Cancer Research.
To identify additional familial pancreatic cancer genes,
researchers recruited study participants enrolled into one of the familial
pancreatic cancer registries participating in the Pancreatic Cancer Genetic
Epidemiology (PACGENE) consortium. Researchers examined the whole-genome
sequences of 16 participants from six families and the whole-exome sequences of
an additional 22 participants from 10 families, each of which included at least
three members with pancreatic ductal adenocarcinoma.
“There was significant reason to believe this
clustering was due to genetics, but we had not, to this point, been able to
find the causative genes that explained the cluster of pancreatic cancer for a
majority of these families,” study researcher Allison Klein, PhD,
associate professor of oncology at the Sidney Kimmel Comprehensive Cancer
Center at Johns Hopkins and director of the National Familial Pancreas Tumor
Registry, said in a press release.
Researchers sequenced the entire coding region of the
ATM gene in an additional 166 familial pancreatic cancer patients —
71 of whom were from relatives with three or more pancreatic cancers — and
190 spouse controls to determine the predominance of the deleterious ATM
gene among controls and familial pancreatic cancer patients.
During sequence analysis, researchers identified four
additional patients (2.4%) with deleterious mutations in the ATM gene,
yet none in the 190 spouse controls (P=.046). When researchers focused
on only the most severely affected families with three or more pancreatic
cancer cases, it was found that 4.6% carried deleterious ATM gene
Disclosure: Researchers report licensing
agreements and royalty shares with Myriad Genetics Inc., Inostics, PGDx and