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Detection of occult high graded microsatellite instabilities in MMR gene mutation negative HNPCC tumors by addition of complementary marker analysis.
Eur J Med Res. 2005 Jan 28; 10(1):23-8.EJ

Abstract

BACKGROUND

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant tumor syndrome predisposing to predominantly colorectal and endometrial cancer. In 90% of the cases, molecular analyses reveal microsatellite instabilities due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2, among these tumors.

PATIENTS AND METHODS

Tumors from 40 HNPCC index patients (31 Amsterdam positive, 9 Bethesda positive; 21 females, 19 males; mean age 48.0 +/- 13.2 years) were examined. In contrast to the classical constellation, their tumors revealed only a microsatellite stable (MSS, n=31)--or low instable (MSI-L, n=9)--tumor phenotype following the international reference panel of 5 microsatellites. No MLH1 and MSH2 mutations were detectable. Complementary microsatellites (BAT40, D10S197, D13S153, D18S58, MYCL1) were investigated by PCR and fragment analysis to find other instabilities which might hint to the MIN-pathway of the tumors.

RESULTS

Due to ten microsatellites in total tumors were now reclassified in 4 MSI-H (10%), 24 MSI-L (60%) and 12 in MSS (30%) phenotypes. The mean age of onset for CRCs was the lowest in the MSI-H group with 45.7 +/- 9.6 years (vs. 48.7 +/- 14.3 and 49.0 +/- 12.9 years in MSI-L and MSS group). MSI-H-and MSI-L tumors were often localized in the proximal colon (50 and 52%), whereas MSS tumors were preferentially localized in the distal colon (77%). -

CONCLUSION

Complementary microsatellites help to subdive "non-classical" HNPCC in subgroups with different clinical appearance. It allows to detect occult MSI-H tumors with up to 10% and to confirm MSS tumors who seem to have a similar biological behaviour like sporadic CRC. Maybe that this genetic reclassification influence the decision of whether to offer patients chemotherapy or not, since it is known that patients with instable tumors do not benefit from chemotherapy as well as patients with microsatellite stable tumors.

Authors+Show Affiliations

Medizinsche Klinik und Poliklinik, Ludwig-Maximilians-Universität, München, Germany. Uwe.Schiemann@insel.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15737950

Citation

Schiemann, U, et al. "Detection of Occult High Graded Microsatellite Instabilities in MMR Gene Mutation Negative HNPCC Tumors By Addition of Complementary Marker Analysis." European Journal of Medical Research, vol. 10, no. 1, 2005, pp. 23-8.
Schiemann U, Müller-Koch Y, Gross M, et al. Detection of occult high graded microsatellite instabilities in MMR gene mutation negative HNPCC tumors by addition of complementary marker analysis. Eur J Med Res. 2005;10(1):23-8.
Schiemann, U., Müller-Koch, Y., Gross, M., Glas, J., Baretton, G., Muders, M., Mussack, T., & Holinski-Feder, E. (2005). Detection of occult high graded microsatellite instabilities in MMR gene mutation negative HNPCC tumors by addition of complementary marker analysis. European Journal of Medical Research, 10(1), 23-8.
Schiemann U, et al. Detection of Occult High Graded Microsatellite Instabilities in MMR Gene Mutation Negative HNPCC Tumors By Addition of Complementary Marker Analysis. Eur J Med Res. 2005 Jan 28;10(1):23-8. PubMed PMID: 15737950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detection of occult high graded microsatellite instabilities in MMR gene mutation negative HNPCC tumors by addition of complementary marker analysis. AU - Schiemann,U, AU - Müller-Koch,Y, AU - Gross,M, AU - Glas,J, AU - Baretton,G, AU - Muders,M, AU - Mussack,T, AU - Holinski-Feder,E, PY - 2005/3/2/pubmed PY - 2005/4/9/medline PY - 2005/3/2/entrez SP - 23 EP - 8 JF - European journal of medical research JO - Eur. J. Med. Res. VL - 10 IS - 1 N2 - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant tumor syndrome predisposing to predominantly colorectal and endometrial cancer. In 90% of the cases, molecular analyses reveal microsatellite instabilities due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2, among these tumors. PATIENTS AND METHODS: Tumors from 40 HNPCC index patients (31 Amsterdam positive, 9 Bethesda positive; 21 females, 19 males; mean age 48.0 +/- 13.2 years) were examined. In contrast to the classical constellation, their tumors revealed only a microsatellite stable (MSS, n=31)--or low instable (MSI-L, n=9)--tumor phenotype following the international reference panel of 5 microsatellites. No MLH1 and MSH2 mutations were detectable. Complementary microsatellites (BAT40, D10S197, D13S153, D18S58, MYCL1) were investigated by PCR and fragment analysis to find other instabilities which might hint to the MIN-pathway of the tumors. RESULTS: Due to ten microsatellites in total tumors were now reclassified in 4 MSI-H (10%), 24 MSI-L (60%) and 12 in MSS (30%) phenotypes. The mean age of onset for CRCs was the lowest in the MSI-H group with 45.7 +/- 9.6 years (vs. 48.7 +/- 14.3 and 49.0 +/- 12.9 years in MSI-L and MSS group). MSI-H-and MSI-L tumors were often localized in the proximal colon (50 and 52%), whereas MSS tumors were preferentially localized in the distal colon (77%). - CONCLUSION: Complementary microsatellites help to subdive "non-classical" HNPCC in subgroups with different clinical appearance. It allows to detect occult MSI-H tumors with up to 10% and to confirm MSS tumors who seem to have a similar biological behaviour like sporadic CRC. Maybe that this genetic reclassification influence the decision of whether to offer patients chemotherapy or not, since it is known that patients with instable tumors do not benefit from chemotherapy as well as patients with microsatellite stable tumors. SN - 0949-2321 UR - https://www.unboundmedicine.com/medline/citation/15737950/Detection_of_occult_high_graded_microsatellite_instabilities_in_MMR_gene_mutation_negative_HNPCC_tumors_by_addition_of_complementary_marker_analysis_ DB - PRIME DP - Unbound Medicine ER -