E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.
To extend earlier observations of germline E-cadherin mutations in kindreds with an inherited susceptibility to diffuse gastric cancer, we searched for germline E-cadherin mutations in five further families affected predominantly by diffuse gastric cancer and one family with a history of diffuse gastric cancer and early-onset breast cancer. Heterozygous inactivating mutations were found in the E-cadherin gene in each of these families. No mutation hotspots were identified. These results demonstrate that germline mutation of the E-cadherin gene is a common cause of hereditary diffuse gastric cancer and suggest a role for these mutations in the incidence of breast cancer.
Guilford
P J
PJ
Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin, New Zealand. parry.guilford@otago.ac.nz
Hopkins
J B
JB
Grady
W M
WM
Markowitz
S D
SD
Willis
J
J
Lynch
H
H
Rajput
A
A
Wiesner
G L
GL
Lindor
N M
NM
Burgart
L J
LJ
Toro
T T
TT
Lee
D
D
Limacher
J M
JM
Shaw
D W
DW
Findlay
M P
MP
Reeve
A E
AE
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007962:Leukocytes; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*; D013577:Syndrome
D015820:Cadherins