42 Abstract # 15 <strong>Mitochondrial</strong> DNA genotyping and methodological approaches to quantify heteroplasmy of mitochondrial mutations reveal synchronous nature of simultaneously detected endometrial and ovarian cancers Girolimetti G 1 ., Guerra F 1 ., Kurelac I 1 ., Perrone A.M 1 ., Procaccini M 1 ., De Biase D 2 ., Ceccarelli C 1 ., Caprara G 1 ., De Iaco P 1 ., Santini D 1 ., Gasparre G 1 . 1 Dip. Sc. Mediche e Chirurgiche-DIMEC, U.O. Genetica Medica, Policlinico S.Orsola-Malpighi, Bologna, Italy. 2 Dip Ematologia e Scienze Oncologiche “L. & A. Seragnoli”, Ospedale Bellaria, Bologna, Italy. Background Simultaneous independent primary tumors of the female genital tract occur in 1–2% of gynecological cancer patients. Guidelines for determining the nature of simultaneously detected tumors are often ambiguous and may require further molecular analyses 1 . We demonstrated in a previous case of synchronous endometrial (EC) and ovarian carcinoma (OC) the important role of mitochondrial DNA (mtDNA) sequencing in diagnosis 2 . In fact, it is plausible to think that the detection of a random somatic mtDNA mutation in both EC and OC of the same patient may be considered as an unequivocal marker of clonality of the two lesions, since it is virtually impossible that the same mutation may arise in two independent tumors. When investigating mtDNA mutations, the peculiar aspects of mitochondrial genetics, such as heteroplasmy, require suitable approaches which must be sensitive enough to detect low mutation loads 3 . Objectives We aim to demonstrate how the use of mtDNA mutations screening for diagnosis of synchrony in simultaneously diagnosed EC and OC may be informative when the usual guideline approaches are unsuccessful. Methods <strong>Mitochondrial</strong> DNA sequencing was performed in 11 samples of women with suspected synchronous cancer. In order to establish the tumor specificity and the heteroplasmy level of the mutations, different methods were used: Fluorescent PCR (F-PCR), denaturing High Performance Liquid Chromatography (dHPLC), quantitative Real-Time PCR (qRTPCR). Results <strong>Mitochondrial</strong> tumor specific mutations at different heteroplasmy levels were found in 5/11 cases therefore this analysis was informative for 45% of patients. In these 5 women mtDNA analysis indicated metastatic cancer diagnosis (Figure). Conclusion <strong>Mitochondrial</strong> DNA sequencing supported by more sensitive approaches to detect lowlevel heteroplasmy may provide a cheap and useful contribution to indisputably recognize the metastatic nature of simultaneously detected carcinomas. References 1 Singh N, Synchronous tumours of the female genital tract, Histopathology, 56, 277–285, 2010; 2 Guerra F et al., <strong>Mitochondrial</strong> DNA genotyping reveals synchronous nature of simultaneously detected endometrial and ovarian cancers, Gynecol Oncol, 122:457-8, 2011; 3 Kurelac I et al., Searching for a needle in the haystack: Comparing six methods to evaluate heteroplasmy in difficult sequence context, Biotechnology Advances 30 363-371, 2012;
43 Tuesday 27 th Neuro Abstracts # 16 – 23
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