102. Elucidating the genomic landscape of Prostate Adenocarcinoma through whole genome and transcriptome sequencing

Aly Abdelkareem

Marilena Melas

Dr. Marilena Melas is an Assistant Director in Molecular Diagnostics (Oncology) at New York Genome Center since August of 2021. Dr. Melas holds an integrated BS-MSc in Applied Biology & Biotechnology from the University of Ioannina in Greece and two master’s degrees — the first one in Molecular Medicine at the University of Crete, Greece, and the second one in Genetics of Human Diseases at the University College London, UK. Dr. Melas completed her PhD in Cancer Biology and Genomics at the USC Norris Comprehensive Cancer Center/University of Southern California Keck School of Medicine in Los Angeles.

After her PhD, she completed an ABMGG Clinical Laboratory Genetics and Genomics (LGG) fellowship at the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital, affiliated with the Ohio State University. In her current role as a laboratory geneticist, Dr. Melas specializes in cancer genome diagnostics focusing on the analysis, interpretation, and reporting of clinical molecular test results for Oncology Genome and Transcriptome sequencing assays. She serves as a junior member of the Board of Directors of the Cancer Genomics Consortium (CGC), and volunteers as a Communications Committee and Program Committee member at CGC. She is also the communications liaison of the Compendium of Cancer Genome Aberrations (CCGA) and is a member of the Molecular Pathology Competency Working Group of the Association for Molecular Pathology (AMP). Her research interests include the translation of genomic discoveries into clinical and therapeutic applications in the field of personalized medicine, to provide state-of-the-art patient care.


Marilena Melasa, Heather Geigera, Sowmya T. Srinivasaa, Saurav Guhaa, Vanessa Felicea, Lena Fieldinga, Amanda Thomas-Wilsona, Ashley Wilsona, Theresa MacDonaldb, Ryan Smithb, Jyothi Manoharb, Michelle Primianob, Olivier Elementob, Ravi Sharafb, Kazimierz O. Wrzeszczynskib, Vaidehi Jobanputrab

aNew York Genome Center, New York City, NY, USA; bWeill Cornell Medical Center, New York City, NY, USA

Whole Genome and Transcriptome Sequencing (WGTS) testing provides a comprehensive molecular profile of a patient’s tumor. Genome sequencing was performed at the New York Genome Center CLIA laboratory, from frozen and FFPE tumor of two cases diagnosed with prostate adenocarcinoma and matched normal blood DNA. RNA sequencing of the two separate tumors was also performed using NYGC proprietary analysis pipeline. Results of the first specimen showed two biallelic inactivating CDK12 alterations, focal tandem duplications across entire genome and a high rate of DNA fusions likely due to DNA mismatch repair error. WGTS results expanded therapeutic options for this patient, from only PARP inhibitors due to DNA repair defects, to immunotherapy options due to the potential for fusion-induced neoantigens. The second case contained an in-frame FOXA1 deletion reported as oncogenic in various cancer types. FOXA1 was also identified as part of a chromosomal gain on 14q12-q21. A frameshift variant in ATM (p.Met2384fs) was also detected. This alteration has not been reported in COSMIC in any tumor and its biological significance remains uncertain (VUS) for this prostate adenocarcinoma. A treatment option with degarelix + NHT is considered for this case as reinforced by genomic profiling. In both cases, RNA sequencing revealed the same known prostate cancer fusion, SLC45A3::ELK4. Our study describes two cases with different driving alterations in the same cancer type which could only be identified by WGTS, and with different therapeutic options for the same cancer. Our results helped guide patient care by unveiling the genomic spectrum of prostate adenocarcinoma.