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
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