Genomic stratification and liquid biopsy in a rare adrenocortical carcinoma (ACC) case, with dual lung metastases

• DOI: 10.1101/mcs.a003764
• Publication Date: 2019-04-01T18:45:19Z
• Authors: Mark J. McCabe; Mark Pinese; Chia-Ling Chan; Nisa Sheriff; Tanya J. Thompson; John Grady; Marie Wong; Marie-Emilie A. G...; Clare Puttick; Velimir Gayevskiy; Elektra Hajdu; Stephen Q. Wong; Wade Barrett; Peter Earls; Robyn Lukeis; Yuen Y. Cheng; Ruby C.Y. Lin; David M. Thomas; D. Neil Watkins; Marcel E. Dinger; Ann I. McCormack; Mark J. Cowley
• Keywords: Microsatellite Instability; Mitotane; STK11; Liquid biopsy; MSH2

Adrenocortical carcinoma is a rare malignancy with poor prognosis and few treatment options. Molecular characterization of this cancer remains limited. We present case an adrenocortical (ACC) in 37-yr-old female, dual lung metastases identified 1 yr following commencement adjuvant mitotane therapy. As standard therapeutic regimens are often unsuccessful ACC, we undertook comprehensive genomic study into to identify options monitor disease progress. performed targeted whole-genome sequencing germline, primary tumor, both metastatic tumors from patient monitored recurrence over 2 years using liquid biopsy for ctDNA steroid hormone measurements. Sequencing revealed the were hyperhaploid, extensive loss heterozygosity but structural rearrangements. Loss-of-function mutations MSH2 , TP53 RB1 PTEN resulting mismatch repair signatures microsatellite instability. At cellular level, populated by mitochondria-rich oncocytes. Longitudinal mutation profiles unable detect micrometastatic disease, consistent clinical indicators remission. The molecular our ACC suggested immunotherapy event progression; however, free cancer. analysis presented here could be applied other and/or poorly stratified cancers novel or repurpose existing options, thereby broadly improving diagnoses, treatments, prognoses.