ASCO GU 2019: Whole Genome and Transcriptome Analysis of Metastatic Adrenocortical Carcinoma

San Francisco, CA (  Although adrenal cortical carcinoma (ACC) is a rare malignancy, it is a rather aggressive one, with approximately 40% of patients presenting with metastatic disease. The standard of care treatment is currently a combination of etoposide/doxorubicin/cisplatin (EDP) and mitotane. Unfortunately, ACC has a poor response to cytotoxic treatment and most patients with metastatic disease show progression.  Phase II patients that have evaluated second-line treatments for patients who show progression after EDP + mitotane have been negative, however. In order to better understand what second-line agents may show efficacy in patients with progression, we need to first understand the underlying genetic alterations that drive this malignancy.

As part of the rapid abstract session B at the 2019 Genitourinary Cancers Symposium in San Francisco, Dr. Jean-Michal Lavole, from BC cancer shared his data evaluating the genetic alterations that commonly occur in patients with metastatic ACC (mACC). He and his group sought to characterize the molecular landscape of mACC and to potentially identify novel therapeutic targets. They performed a whole genome and transcriptome analysis of fresh tissue from 6 patients with mACC in order to evaluate for any common genetic mutations.

Using the HRDetect assay, Lavole and his group found several common mutations in DNA repair genes, including BRCA-2, ATM, and FANCA, as well as in certain cell cycle regulatory genes including RB1, and CCNE1. They also found that large-scale chromosomal copy gains and losses were common. Many of these common mutations have also been previously shown in the literature. He believes that this improved understanding of the genetics of mACC may suggest new therapeutic targets for treatment.

Dr. Lavole concluded that although his analysis showed significant heterogeneity between the genetic alterations in patients with mACC, there were a few common mutations, including in CTNBB1 and TP53. His group feels that their findings may suggest some new therapeutic targets for second line treatments. These include DNA damage repair genes and cell cycle regulatory genes. There may be future applications for poly ADP ribose polymerase (PARP) inhibitors, and for cell cycle checkpoint inhibitors, however, more clinical studies are required to understand the effect these medications have.

Presented by: Jean-Michel Lavoie, MD, Department of Medical Oncology, BC Cancer, Vancouver, British Columbia

Written by: Brian Kadow, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

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