Background: Cervical carcinoma (CC) is one of the most common cancers among women worldwide and the first cause of death among the Mexican female population. CC progression shows a continuum of neoplastic transitions until invasion. Matrix metalloproteinases (MMPs) and cathepsins play a central role on the enhancement of tumor-induced angiogenesis, cell migration, proliferation, apoptosis and connective tissue degradation. MMPs -2 and -9 expression has been widely studied in cervical cancer. Nevertheless, no other metalloproteinases or cathepsins have been yet related with the progression and/or invasion of this type of cancer.

Background: Chromosomal Comparative Genomic Hybridization (CGH) has been applied to all stages of cervical carcinoma progression, defining a specific pattern of chromosomal imbalances in this tumor. However, given its limited spatial resolution, chromosomal CGH has offered only general information regarding the possible genetic targets of DNA copy number changes.

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The availability of large numbers of formalin-fixed, paraffin-embedded (FFPE) tumor DNA samples, together with accurate and specific clinical annotations, can be a great resource for in-depth analysis of correlations of somatic and germline DNA alterations with clinical outcome. However, the effects of this tissue preservation technique on next-generation DNA sequencing technologies and downstream analyses are still being investigated. Furthermore, usually the archives of such FFPE samples do not include matched normal tissue, which complicates the process of identifying somatic alterations. We are in the process of analyzing lung adenocarcinoma, colorectal and prostate patient datasets, which contain both an FFPE and a fresh-frozen tumor together with a matched blood normal sample. The availability of both a frozen and an FFPE tumor sample enables us to compare the detected somatic point mutations and indels, taking into account the fact that these pairs are produced from different aliquots of DNA. This analysis includes calculating the power to detect variants in the FFPE sample given that they have been observed in the fresh frozen tumor, as well as the validation rate of clonal SNVs between the two samples. We are also developing a method for classification of SNVs as germline or somatic without a paired normal sample by taking advantage of the fact that most tumor samples contain a substantial fraction of normal cells. Because stromal contamination has a different effect on the allelic fraction of somatic vs. germline SNVs, we can apply algorithms to estimate tumor purity and absolute somatic copy numbers in order to distinguish the two types of events. We present preliminary results from these analyses. Citation Format: Petar Stojanov, Scott L. Carter, Ivan Imaz Rosshandler, Andrey Sivachenko, Alberto Salido Guadarrama, Karla Vazquez, Sandra Romero Cordoba, Kristian Cibulskis, Carrie Sougnez, Douglas Voet, Gordon Saksena, Lee Lichtenstein, Lihua Zou, Scott Frazer, Chip Stewart, Rameen Beroukhim, Matthew Meyerson, Michael S. Lawrence, Gad Getz. Analysis of formalin-fixed paraffin-embedded (FFPE) samples. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5135. doi:10.1158/1538-7445.AM2013-5135