The genetics of HNPCC:: Application to diagnosis and screening

被引:71
作者
Abdel-Rahman, Wael M.
Mecklin, Jukka-Pekka
Peltomaki, Paivi
机构
[1] Univ Helsinki, Biomedicum Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland
[2] Jyvaskyla Cent Hosp, Dept Surg, Jyvaskyla, Finland
关键词
colorectal cancer; HNPCC; Lynch syndrome; mismatch repair; microsatellite instability; Muir-Torre syndrome; Turcot's syndrome;
D O I
10.1016/j.critrevonc.2005.11.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hereditary nonpolyposis colorectal cancer syndrome (HNPCC; Lynch Syndrome) is the most common form of hereditary colorectal cancers. Predisposed individuals have increased lifetime risk of developing colorectal, endometrial and other cancers. The syndrome is primarily due to heterozygous germline mutations in one of the mismatch repair genes; mainly MLH1, MSH2, MSH6 and PMS2. The resulting mismatch repair deficiency leads to microsatellite instability which is the hallmark of tumors arising within this syndrome, as well as a variable proportion of sporadic tumors. Diagnostic guidelines and criteria for molecular testing of suspected families have been proposed and are continuously updated. However, not all families fulfilling these criteria show mutations in mismatch repair genes and/or microsatellite instability implicating other, as yet unknown, carcinogenic mechanisms and predisposition genes. This subset of tumors is the focus of current clinical and molecular research. This review addresses recent advances in the field of HNPCC research and their applications in the management of affected individuals and families. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:208 / 220
页数:13
相关论文
共 141 条
  • [41] Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: Later age of onset
    Hampel, H
    Stephens, JA
    Pukkala, E
    Sankila, R
    Aaltonen, LA
    Mecklin, JP
    de la Chapelle, A
    [J]. GASTROENTEROLOGY, 2005, 129 (02) : 415 - 421
  • [42] Screening for the Lynch syndrome (Hereditary nonpolyposis colorectal cancer).
    Hampel, H
    Frankel, WL
    Martin, E
    Arnold, M
    Khanduja, K
    Kuebler, P
    Nakagawa, H
    Sotamaa, K
    Prior, TW
    Westman, J
    Panescu, J
    Fix, D
    Lockman, J
    Comeras, I
    de la Chapelle, A
    Ellison, C
    Melvin, S
    Winston, J
    Adeli, A
    Burak, W
    Chadwick, R
    Elkhatib, I
    Hemingway, T
    Jamieson, K
    Johnson, C
    LaJeunesse, J
    Liyanarachchi, S
    Rangel, P
    Soble, D
    Walker, M
    Wise, T
    Zhang, Y
    Schlanger, R
    Aguilar, P
    Hura, D
    Keith, J
    Kerner, B
    Lavalle, G
    Taylor, C
    Vara, T
    Zangmeister, J
    DeVictor, S
    Hines, L
    Lindsey, M
    Madhavan, J
    Padmanabhan, A
    Hamelberg, K
    Niemann, T
    Behrens, BC
    Blair, SC
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (18) : 1851 - 1860
  • [43] A homozygous mutation in MSH6 causes Turcot syndrome
    Hegde, MR
    Chong, B
    Blazo, ME
    Chin, LHE
    Ward, PA
    Chintagumpala, MM
    Kim, JY
    Plon, SE
    Richards, CS
    [J]. CLINICAL CANCER RESEARCH, 2005, 11 (13) : 4689 - 4693
  • [44] LOSS OF THE WILD-TYPE MLH1 GENE IS A FEATURE OF HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER
    HEMMINKI, A
    PELTOMAKI, P
    MECKLIN, JP
    JARVINEN, H
    SALOVAARA, R
    NYSTROMLAHTI, M
    DELACHAPELLE, A
    AALTONEN, LA
    [J]. NATURE GENETICS, 1994, 8 (04) : 405 - 410
  • [45] Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations:: Impact on counseling and surveillance
    Hendriks, YMC
    Wagner, A
    Morreau, H
    Menko, F
    Stormorken, A
    Quehenberger, F
    Sandkuijl, L
    Moller, P
    Genuardi, M
    Van Houwelingen, H
    Tops, C
    Van Puijenbroek, M
    Verkuijlen, P
    Kenter, G
    Van Mil, A
    Meijers-Heijboer, H
    Tan, GB
    Breuning, MH
    Fodde, R
    Wijnen, JT
    Bröcker-Vriends, AHJT
    Vasen, H
    [J]. GASTROENTEROLOGY, 2004, 127 (01) : 17 - 25
  • [46] Little evidence for involvement of MLH3 in colorectal cancer predisposition
    Hienonen, T
    Laiho, P
    Salovaara, R
    Mecklin, JP
    Järvinen, H
    Sistonen, P
    Peltomäki, P
    Lehtonen, R
    Nupponen, NN
    Launonen, V
    Karhu, A
    Aaltonen, LA
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2003, 106 (02) : 292 - 296
  • [47] *INT AG RES CANC, GLOBC 2002 DAT
  • [48] UBIQUITOUS SOMATIC MUTATIONS IN SIMPLE REPEATED SEQUENCES REVEAL A NEW MECHANISM FOR COLONIC CARCINOGENESIS
    IONOV, Y
    PEINADO, MA
    MALKHOSYAN, S
    SHIBATA, D
    PERUCHO, M
    [J]. NATURE, 1993, 363 (6429) : 558 - 561
  • [49] Jagmohan-Changur S, 2003, CANCER RES, V63, P154
  • [50] Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer
    Järvinen, HJ
    Aarnio, M
    Mustonen, H
    Aktan-Collan, K
    Aaltonen, LA
    Peltomäki, P
    de la Chapelle, A
    Mecklin, JP
    [J]. GASTROENTEROLOGY, 2000, 118 (05) : 829 - 834