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. 2004 Jun 24:5:16.
doi: 10.1186/1471-2350-5-16.

HNPCC: six new pathogenic mutations

Erdmute Kunstmann  1 , Judith Vieland, Frank E Brasch, Stephan A Hahn, Joerg T Epplen, Karsten Schulmann, Wolff Schmiegel
Affiliations

HNPCC: six new pathogenic mutations

Erdmute Kunstmann et al. BMC Med Genet. .

Abstract

Background: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease with a high risk for colorectal and endometrial cancer caused by germline mutations in DNA mismatch-repair genes (MMR). HNPCC accounts for approximately 2 to 5% of all colorectal cancers. Here we present 6 novel mutations in the DNA mismatch-repair genes MLH1, MSH2 and MSH6.

Methods: Patients with clinical diagnosis of HNPCC were counselled. Tumor specimen were analysed for microsatellite instability and immunohistochemistry for MLH1, MSH2 and MSH6 protein was performed. If one of these proteins was not detectable in the tumor mutation analysis of the corresponding gene was carried out.

Results: We identified 6 frameshift mutations (2 in MLH1, 3 in MSH2, 1 in MSH6) resulting in a premature stop: two mutations in MLH1 (c.2198_2199insAACA [p.N733fsX745], c.2076_2077delTG [p.G693fsX702]), three mutations in MSH2 (c.810_811delGT [p.C271fsX282], c.763_766delAGTGinsTT [p.F255fsX282], c.873_876delGACT [p.L292fsX298]) and one mutation in MSH6 (c.1421_1422dupTG [p.C475fsX480]). All six tumors tested for microsatellite instability showed high levels of microsatellite instability (MSI-H).

Conclusions: HNPCC in families with MSH6 germline mutations may show an age of onset that is comparable to this of patients with MLH1 and MSH2 mutations.

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Figures

Figure 1
Figure 1
MLH1 staining Patient 0660-6: Mucinous adenocarcinoma of the colon with a strong nuclear staining (red staining product) of the tumor cells (arrows) for MLH1 (1).
Figure 2
Figure 2
MSH2 staining Patient 0660-6: Mucinous adenocarcinoma of the colon with a negative staining of the tumor cells for MSH2. As an internal positive control, lymphocytes (arrowheads) in an adjacent lymph follicle show a positive nuclear staining for MSH2
Figure 3
Figure 3
MSH6 staining Patient 0660-6: Mucinous adenocarcinoma of the colon with a negative staining of the tumor cells for MSH6. As an internal positive control, lymphocytes (arrowheads) in an adjacent lymph follicle show a positive nuclear staining for MSH6
See this image and copyright information in PMC

References

    1. Grady WM. Genetic testing for high-risk colon cancer patients. Gastroenterol. 2003;124:1574–1594. doi: 10.1016/S0016-5085(03)00376-7. - DOI - PubMed
    1. Liu B, Parsons R, Papadopoulos N, Nicolaides NC, Lynch HT, Watson P, Jass JR, Dunlop M, Wyllie A, Peltomaki P, de la Chapelle A, Hamilton SR, Vogelstein B, Kinzler KW. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med. 1996;2:169–174. - PubMed
    1. Kolodner RD, Tytell JD, Schmeits JL, Kane MF, Gupta RD, Weger J, Wahlberg S, Fox EA, Peel D, Ziogas A, Garber JE, Syngal S, Anton-Culver H, Li FP. Germ-line msh6 mutations in colorectal cancer families. Cancer Res. 1999;59:5068–5074. - PubMed
    1. Wu Y, Berends MJ, Mensink RG, Kempinga C, Sijmons RH, van Der Zee AG, Hollema H, Kleibeuker JH, Buys CH, Hofstra RM. Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations. Am J Hum Genet. 1999;65:1291–1298. doi: 10.1086/302612. - DOI - PMC - PubMed
    1. Wijnen J, de Leeuw W, Vasen H, van der Klift H, Moller P, Stormorken A, Meijers-Heijboer H, Lindhout D, Menko F, Vossen S, Moslein G, Tops C, Brocker-Vriends A, Wu Y, Hofstra R, Sijmons R, Cornelisse C, Morreau H, Fodde R. Familial endometrial cancer in female carriers of MSH6 germline mutations. Nat Genet. 1999;23:142–144. doi: 10.1038/13773. - DOI - PubMed

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