Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Somatic molecular alterations in ovarian cancer

LL Hansen PhD 1, MC Psaroudi PhD 4, C Dimitrakakis MD 5, L Zhen MS 3, S Michalas MD 5, F Gilbert MD 3, FA Chervenak MD 2, HRK Barber MD 2, II Arzimanoglou PhD 2

1 Institute of Human Genetics, University of Aarhus, Aarhus DK-8000, Denmark, 2 Dept Obstetrics & Gynecology,, 3 Div of Human Genetics, Cornell University/Weill Medical College, New York, NY, 4 Laboratory of Chemical Carcinogenesis, Institute of Biological Research and Biotechnology, National Hellenic Research Fndn;,

AIM: To detect somatic molecular alterations such as coding DNA instability, loss of heterozygosity (LOH), and mutations specific for ovarian cancer (OC). METHODS: A combination of high resolution GeneScanTM software analysis and cloning into PCR-Script TM Amp SK(+) followed by automated DNA sequencing. The sensitivity of our GeneScanTM system has been enhanced to the point to consistently detect single base changes, as confirmed by sequencing. RESULTS: Negligible coding instability and very few somatic mutations were found in selected sequences of mismatch DNA repair genes. In contrast, LOH confined to the tumor was frequently found in about 40-50% of the informative OC cases, for either the hMSH3 or hMLH1 gene, and for the chromosomal sites 13q12, and 16q23. The last two sites were examined because our previous work in breast cancer indicated that LOH at 16q23 is associated with good prognosis, and at 13q12 (BRCA2 region) is highly specific for this type of cancer. CONCLUSIONS: Our findings clearly suggest a major role for LOH as a mechanism responsible for the inactivation of genes during the progressive development of ovarian cancer. They also suggest that somatic changes affecting the coding region of genes are likely to occur rarely in OC.

KEY WORDS: Ovarian tumor, somatic mutations, DNA instability, GeneScanTM.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic instability.