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.

Jae-Gahb Park; Duck-Woo Kim; Chang Won Hong; Byung-Ho Nam; Young-Kyoung Shin; Sung-Hye Hong; Il-Jin Kim; Seok-Byung Lim; Melyssa Aronson; Marie Luise Bisgaard; Gregor J Brown; John Burn; Elizabeth Chow; Peggy Conrad; Fiona Douglas; Malcolm Dunlop; James Ford; Marc S Greenblatt; Jarvinen Heikki; Karl Heinimann; Elly L Lynch; Finlay Macrae; Wendy C McKinnon; Gabriela Möeslein; Benedito Mauro Rossi; Paul Rozen; Lyn Schofield; Carlos Vaccaro; Hans Vasen; Mary Velthuizen; Alessandra Viel; Juul Wijnen; International Society for Gastrointestinal Hereditary Tumours

doi:10.1158/1078-0432.CCR-05-2452

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.

Jae-Gahb Park, Duck-Woo Kim, Chang Won Hong, Byung-Ho Nam, Young-Kyoung Shin, Sung-Hye Hong, Il-Jin Kim, Seok-Byung Lim, Melyssa Aronson, Marie Luise Bisgaard, Gregor J Brown, John Burn, Elizabeth Chow, Peggy Conrad, Fiona Douglas, Malcolm Dunlop, James Ford, Marc S Greenblatt, Jarvinen Heikki, Karl HeinimannElly L Lynch, Finlay Macrae, Wendy C McKinnon, Gabriela Möeslein, Benedito Mauro Rossi, Paul Rozen, Lyn Schofield, Carlos Vaccaro, Hans Vasen, Mary Velthuizen, Alessandra Viel, Juul Wijnen, International Society for Gastrointestinal Hereditary Tumours

Department of Cellular and Molecular Medicine

35 Citations (Scopus)

Abstract

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).

Original language	English
Journal	Clinical Cancer Research
Volume	12
Issue number	11 Pt 1
Pages (from-to)	3389-93
Number of pages	4
ISSN	1078-0432
DOIs	https://doi.org/10.1158/1078-0432.CCR-05-2452
Publication status	Published - 2006

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Park, J.-G., Kim, D.-W., Hong, C. W., Nam, B.-H., Shin, Y.-K., Hong, S.-H., Kim, I.-J., Lim, S.-B., Aronson, M., Bisgaard, M. L., Brown, G. J., Burn, J., Chow, E., Conrad, P., Douglas, F., Dunlop, M., Ford, J., Greenblatt, M. S., Heikki, J., ... International Society for Gastrointestinal Hereditary Tumours (2006). 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. Clinical Cancer Research, 12(11 Pt 1), 3389-93. https://doi.org/10.1158/1078-0432.CCR-05-2452

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. / Park, Jae-Gahb; Kim, Duck-Woo; Hong, Chang Won et al.
In: Clinical Cancer Research, Vol. 12, No. 11 Pt 1, 2006, p. 3389-93.

Research output: Contribution to journal › Journal article › Research › peer-review

Park, J-G, Kim, D-W, Hong, CW, Nam, B-H, Shin, Y-K, Hong, S-H, Kim, I-J, Lim, S-B, Aronson, M, Bisgaard, ML, Brown, GJ, Burn, J, Chow, E, Conrad, P, Douglas, F, Dunlop, M, Ford, J, Greenblatt, MS, Heikki, J, Heinimann, K, Lynch, EL, Macrae, F, McKinnon, WC, Möeslein, G, Rossi, BM, Rozen, P, Schofield, L, Vaccaro, C, Vasen, H, Velthuizen, M, Viel, A, Wijnen, J & International Society for Gastrointestinal Hereditary Tumours 2006, '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.', Clinical Cancer Research, vol. 12, no. 11 Pt 1, pp. 3389-93. https://doi.org/10.1158/1078-0432.CCR-05-2452

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title = "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.",

abstract = "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).",

author = "Jae-Gahb Park and Duck-Woo Kim and Hong, {Chang Won} and Byung-Ho Nam and Young-Kyoung Shin and Sung-Hye Hong and Il-Jin Kim and Seok-Byung Lim and Melyssa Aronson and Bisgaard, {Marie Luise} and Brown, {Gregor J} and John Burn and Elizabeth Chow and Peggy Conrad and Fiona Douglas and Malcolm Dunlop and James Ford and Greenblatt, {Marc S} and Jarvinen Heikki and Karl Heinimann and Lynch, {Elly L} and Finlay Macrae and McKinnon, {Wendy C} and Gabriela M{\"o}eslein and Rossi, {Benedito Mauro} and Paul Rozen and Lyn Schofield and Carlos Vaccaro and Hans Vasen and Mary Velthuizen and Alessandra Viel and Juul Wijnen and {International Society for Gastrointestinal Hereditary Tumours}",

note = "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",

year = "2006",

doi = "10.1158/1078-0432.CCR-05-2452",

language = "English",

volume = "12",

pages = "3389--93",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research (A A C R)",

number = "11 Pt 1",

}

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 -