Molecular profiles of response to neoadjuvant chemoradiotherapy in oesophageal cancers to develop personalized treatment strategies
Autor: | Henk M.W. Verheul, Nicole C.T. van Grieken, Rosa T. van der Kaaij, Adam J. Bass, Jurriën Stiekema, Victor L. J. L. Thijssen, Leonie K. de Klerk, Donald L. van der Peet, Aaron R. Thorner, Roy L. J. van Wanrooij, Manon van Engeland, Sarah Derks, Arantza Farina Sarasqueta, Johanna W. van Sandick, Maarten A. J. M. Jacobs, Ruben S. A. Goedegebuure, Annemieke Cats |
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Přispěvatelé: | Pathology, VU University medical center, Internal medicine, CCA - Cancer biology and immunology, Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and hepatology, Surgery, Medical oncology laboratory, Radiation Oncology, RS: GROW - R2 - Basic and Translational Cancer Biology, Pathologie |
Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Oncology Cancer Research PROGNOSIS Esophageal Neoplasms PROTEIN PROGRESSION medicine.disease_cause Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] 0302 clinical medicine Medicine HETEROGENEITY DNA sequencing Precision Medicine Promoter Regions Genetic chemoradiation Research Articles Netherlands Aged 80 and over High-Throughput Nucleotide Sequencing Nuclear Proteins General Medicine Methylation Middle Aged CHEMOTHERAPY Esophageal cancer lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Neoadjuvant Therapy 030220 oncology & carcinogenesis DNA methylation Carcinoma Squamous Cell Molecular Medicine Adenocarcinoma Female KRAS Research Article gene methylation Adult medicine.medical_specialty oesophageal cancer Ubiquitin-Protein Ligases lcsh:RC254-282 Disease-Free Survival Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Internal medicine TP63 Genetics Humans Cyclin-Dependent Kinase Inhibitor p16 Aged Glycoproteins COMPLEX CSMD1 business.industry Tumor Suppressor Proteins DNA Helicases Cancer predictive markers ADENOCARCINOMA Promoter DNA Methylation medicine.disease genetic biomarkers GATA4 Transcription Factor stomatognathic diseases 030104 developmental biology CpG Islands business PREOPERATIVE CHEMORADIOTHERAPY RESISTANCE Transcription Factors |
Zdroj: | Molecular Oncology, 15, 901-914 Molecular oncology, 15(4), 901-914. Elsevier de Klerk, L K, Goedegebuure, R S A, van Grieken, N C T, van Sandick, J W, Cats, A, Stiekema, J, van der Kaaij, R T, Farina Sarasqueta, A, van Engeland, M, Jacobs, M A J M, van Wanrooij, R L J, van der Peet, D L, Thorner, A R, Verheul, H M W, Thijssen, V L J L, Bass, A J & Derks, S 2021, ' Molecular profiles of response to neoadjuvant chemoradiotherapy in oesophageal cancers to develop personalized treatment strategies ', Molecular oncology, vol. 15, no. 4, pp. 901-914 . https://doi.org/10.1002/1878-0261.12907 Molecular Oncology Molecular Oncology, 15, 4, pp. 901-914 Molecular Oncology, Vol 15, Iss 4, Pp 901-914 (2021) |
ISSN: | 1574-7891 |
DOI: | 10.1002/1878-0261.12907 |
Popis: | Identification of molecular predictive markers of response to neoadjuvant chemoradiation could aid clinical decision‐making in patients with localized oesophageal cancer. Therefore, we subjected pretreatment biopsies of 75 adenocarcinoma (OAC) and 16 squamous cell carcinoma (OSCC) patients to targeted next‐generation DNA sequencing, as well as biopsies of 85 OAC and 20 OSCC patients to promoter methylation analysis of eight GI‐specific genes, and subsequently searched for associations with histopathological response and disease‐free (DFS) and overall survival (OS). Thereby, we found that in OAC, CSMD1 deletion (8%) and ETV4 amplification (5%) were associated with a favourable histopathological response, whereas SMURF1 amplification (5%) and SMARCA4 mutation (7%) were associated with an unfavourable histopathological response. KRAS (15%) and GATA4 (7%) amplification were associated with shorter OS. In OSCC, TP63 amplification (25%) and TFPI2 (10%) gene promoter methylation were associated with an unfavourable histopathological response and shorter DFS (TP63) and OS (TFPI2), whereas CDKN2A deletion (38%) was associated with prolonged OS. In conclusion, this study identified candidate genetic biomarkers associated with response to neoadjuvant chemoradiotherapy in patients with localized oesophageal cancer. Using DNA sequencing and methylation panels on pretreatment biopsies, we identified candidate molecular alterations associated with response [tumour regression grade (TRG) or survival] to neoadjuvant chemoradiotherapy in localized oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). These findings may assist approaches to further individualize oesophageal cancer treatment. |
Databáze: | OpenAIRE |
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