TY - JOUR
T1 - Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study.
AU - Park, Jae-Gahb
AU - Kim, Duck-Woo
AU - Hong, Chang Won
AU - Nam, Byung-Ho
AU - Shin, Young-Kyoung
AU - Hong, Sung-Hye
AU - Kim, Il-Jin
AU - Lim, Seok-Byung
AU - Aronson, Melyssa
AU - Bisgaard, Marie Luise
AU - Brown, Gregor J
AU - Burn, John
AU - Chow, Elizabeth
AU - Conrad, Peggy
AU - Douglas, Fiona
AU - Dunlop, Malcolm
AU - Ford, James
AU - Greenblatt, Marc S
AU - Heikki, Jarvinen
AU - Heinimann, Karl
AU - Lynch, Elly L
AU - Macrae, Finlay
AU - McKinnon, Wendy C
AU - Möeslein, Gabriela
AU - Rossi, Benedito Mauro
AU - Rozen, Paul
AU - Schofield, Lyn
AU - Vaccaro, Carlos
AU - Vasen, Hans
AU - Velthuizen, Mary
AU - Viel, Alessandra
AU - Wijnen, Juul
AU - International Society for Gastrointestinal Hereditary Tumours
N1 - Keywords: Adaptor Proteins, Signal Transducing; Adenosine Triphosphatases; Adolescent; Adult; Aged; Aged, 80 and over; Child; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Mismatch Repair; DNA Repair Enzymes; DNA-Binding Proteins; Duodenal Neoplasms; Female; Genotype; Germ-Line Mutation; Humans; Ileal Neoplasms; Jejunal Neoplasms; Male; Middle Aged; MutS Homolog 2 Protein; Neoplasms, Second Primary; Nuclear Proteins; Predictive Value of Tests; Questionnaires
PY - 2006
Y1 - 2006
N2 - PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared the distribution of the mismatch repair mutations in our study population with that in a control group, including all pathogenic mismatch repair mutations of the International Society for Gastrointestinal Hereditary Tumours database (excluding those in our study population). In patients with MSH2 mutations, patients with HNPCC-associated SBCs had fewer mutations in the MutL homologue interaction domain (2.9% versus 19.9%, P = 0.019) but an increased frequency of mutations in codons 626 to 733, a domain that has not previously been associated with a known function, versus the control group (26.5% versus 2.8%, P < 0.001). CONCLUSIONS: In HNPCC patients, SBC can be the first and only cancer and may develop as soon as the early teens. The distribution of MSH2 mutations found in patients with HNPCC-associated SBCs significantly differed from that found in the control group (P < 0.001).
AB - PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared the distribution of the mismatch repair mutations in our study population with that in a control group, including all pathogenic mismatch repair mutations of the International Society for Gastrointestinal Hereditary Tumours database (excluding those in our study population). In patients with MSH2 mutations, patients with HNPCC-associated SBCs had fewer mutations in the MutL homologue interaction domain (2.9% versus 19.9%, P = 0.019) but an increased frequency of mutations in codons 626 to 733, a domain that has not previously been associated with a known function, versus the control group (26.5% versus 2.8%, P < 0.001). CONCLUSIONS: In HNPCC patients, SBC can be the first and only cancer and may develop as soon as the early teens. The distribution of MSH2 mutations found in patients with HNPCC-associated SBCs significantly differed from that found in the control group (P < 0.001).
U2 - 10.1158/1078-0432.CCR-05-2452
DO - 10.1158/1078-0432.CCR-05-2452
M3 - Journal article
C2 - 16740762
SN - 1078-0432
VL - 12
SP - 3389
EP - 3393
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11 Pt 1
ER -
