Multiple germline sequence variants with potential cancer risk uncovered by exome sequencing in an anatomic lab donor cadaver with multiple cancer lesions

Abstract

Ovarian cancer is the leading cause of death among gynecological cancers in most developed countries, with many patients developing chemotherapy resistance leaving them with a 5-year survival rate of < 35 %. This dismal overall survival is likely due to the histologic subtype of ovarian carcinoma, advanced stage at diagnosis, and patients developing chemotherapy resistance. Around 20–25 % of women who develop ovarian cancer have a hereditary predisposition to ovarian cancer due to germline mutations in the context of cancer syndromes such as Hereditary Breast and Ovarian Cancer syndrome (HBOC) and Lynch syndrome. These conditions are responsible for around 15 % and 2 % of ovarian cancers, respectively, and predispose individuals to cancer and often at an earlier age. In our study, an anatomical donor whose volunteered medical history described ovarian cancer as the cause of death was found to have multiple metastatic sites, enlarged lymph nodes, total colectomy, and total hysterectomy with bilateral salpingo-oophorectomy upon student dissection. Based on the pathological exam and available medical history, we hypothesized that the donor had an inherited cancer syndrome. To test this hypothesis, we collected multiple tissue samples from this donor which were stained with hematoxylin and eosin (H&E), immunohistochemistry (IHC) techniques, and underwent DNA exome sequencing. Upon completion of our project, we did not discover established germ-line mutations that predispose patients to inherited cancer syndromes. Interestingly, we did find pathogenic mutations in PTPRJ, TLR5, and XRCC3 which have been associated with an increased risk for distinct types of cancer other than colon or ovarian hereditary cancers. More research is needed to determine if mutations in these genes may predispose patients to colon or ovarian cancers. Since these mutations are yet to be implicated with hereditary cancer syndromes, we conclude from our H&E and immunohistochemistry staining, and exome sequencing results, that our subject had primary ovarian cancer that metastasized to her liver, gastrointestinal lymph nodes, and right lung in addition to colonic pathology that required total colectomy.

Keywords

• Hereditary cancer syndromes
• Whole exome sequencing
• Immunohistochemistry
• Ovarian cancer