Detecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma
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...
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MDPI AG
2019-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/5/736 |
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| author | Michael Davidson Louise J. Barber Andrew Woolston Catherine Cafferkey Sonia Mansukhani Beatrice Griffiths Sing-Yu Moorcraft Isma Rana Ruwaida Begum Ioannis Assiotis Nik Matthews Sheela Rao David Watkins Ian Chau David Cunningham Naureen Starling Marco Gerlinger |
| author_facet | Michael Davidson Louise J. Barber Andrew Woolston Catherine Cafferkey Sonia Mansukhani Beatrice Griffiths Sing-Yu Moorcraft Isma Rana Ruwaida Begum Ioannis Assiotis Nik Matthews Sheela Rao David Watkins Ian Chau David Cunningham Naureen Starling Marco Gerlinger |
| author_sort | Michael Davidson |
| collection | DOAJ |
| description | 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. |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:08:23Z |
| publishDate | 2019-05-01 |
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| series | Cancers |
| spelling | doaj.art-affa171323ed40398002f2b5888936352023-09-02T23:19:06ZengMDPI AGCancers2072-66942019-05-0111573610.3390/cancers11050736cancers11050736Detecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric AdenocarcinomaMichael Davidson0Louise J. Barber1Andrew Woolston2Catherine Cafferkey3Sonia Mansukhani4Beatrice Griffiths5Sing-Yu Moorcraft6Isma Rana7Ruwaida Begum8Ioannis Assiotis9Nik Matthews10Sheela Rao11David Watkins12Ian Chau13David Cunningham14Naureen Starling15Marco Gerlinger16Gastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKTranslational Oncogenomics Laboratory, Centre for Evolution and Cancer, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UKTranslational Oncogenomics Laboratory, Centre for Evolution and Cancer, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKTranslational Oncogenomics Laboratory, Centre for Evolution and Cancer, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UKTranslational Oncogenomics Laboratory, Centre for Evolution and Cancer, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKTranslational Oncogenomics Laboratory, Centre for Evolution and Cancer, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UKTranslational Oncogenomics Laboratory, Centre for Evolution and Cancer, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKGastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, Sutton, London SM2 5PT, UKDNA 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.https://www.mdpi.com/2072-6694/11/5/736oesophagogastric adenocarcinomacirculating tumour DNAsomatic copy number aberrationliquid biopsy |
| spellingShingle | Michael Davidson Louise J. Barber Andrew Woolston Catherine Cafferkey Sonia Mansukhani Beatrice Griffiths Sing-Yu Moorcraft Isma Rana Ruwaida Begum Ioannis Assiotis Nik Matthews Sheela Rao David Watkins Ian Chau David Cunningham Naureen Starling Marco Gerlinger Detecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma Cancers oesophagogastric adenocarcinoma circulating tumour DNA somatic copy number aberration liquid biopsy |
| title | Detecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma |
| title_full | Detecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma |
| title_fullStr | Detecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma |
| title_full_unstemmed | Detecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma |
| title_short | Detecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma |
| title_sort | detecting and tracking circulating tumour dna copy number profiles during first line chemotherapy in oesophagogastric adenocarcinoma |
| topic | oesophagogastric adenocarcinoma circulating tumour DNA somatic copy number aberration liquid biopsy |
| url | https://www.mdpi.com/2072-6694/11/5/736 |
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