Detecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma

Cancers

David Cunningham¹  David Watkins¹  Isma Rana¹  Naureen Starling¹  Michael Davidson¹  Catherine Cafferkey¹  Ian Chau¹  Marco Gerlinger¹  Ruwaida Begum¹  Sing-Yu Moorcraft¹  Sheela Rao¹  Ioannis Assiotis²  Andrew Woolston²  Sonia Mansukhani²  Nik Matthews²  Beatrice Griffiths²  LouiseJ. Barber² 

[1] Gastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UK;Translational Oncogenomics Laboratory, Centre for Evolution and Cancer, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK;

关键词: oesophagogastric adenocarcinoma;    circulating tumour DNA;    somatic copy number aberration;    liquid biopsy;   

DOI  :  10.3390/cancers11050736

来源: DOAJ

【 摘 要 】

DNA somatic copy number aberrations (SCNAs) are key drivers in oesophagogastric adenocarcinoma (OGA). Whether minimally invasive SCNA analysis of circulating tumour (ct)DNA can predict treatment outcomes and reveal how SCNAs evolve during chemotherapy is unknown. We investigated this by low-coverage whole genome sequencing (lcWGS) of ctDNA from 30 patients with advanced OGA prior to first-line chemotherapy and on progression. SCNA profiles were detectable pretreatment in 23/30 (76.7%) patients. The presence of liver metastases, primary tumour in situ, or of oesophageal or junctional tumour location predicted for a high ctDNA fraction. A low ctDNA concentration associated with significantly longer overall survival. Neither chromosomal instability metrics nor ploidy correlated with chemotherapy outcome. Chromosome 2q and 8p gains before treatment were associated with chemotherapy responses. lcWGS identified all amplifications found by prior targeted tumour tissue sequencing in cases with detectable ctDNA as well as finding additional changes. SCNA profiles changed during chemotherapy, indicating that cancer cell populations evolved during treatment; however, no recurrent SCNA changes were acquired at progression. Tracking the evolution of OGA cancer cell populations in ctDNA is feasible during chemotherapy. The observation of genetic evolution warrants investigation in larger series and with higher resolution techniques to reveal potential genetic predictors of response and drivers of chemotherapy resistance. The presence of liver metastasis is a potential biomarker for the selection of patients with high ctDNA content for such studies.

【 授权许可】

Unknown