TY - JOUR
T1 - Molecular profiles of response to neoadjuvant chemoradiotherapy in oesophageal cancers to develop personalized treatment strategies
AU - de Klerk, Leonie K.
AU - Goedegebuure, Ruben S. A.
AU - van Grieken, Nicole C. T.
AU - van Sandick, Johanna W.
AU - Cats, Annemieke
AU - Stiekema, Jurrien
AU - van der Kaaij, Rosa T.
AU - Farina Sarasqueta, Arantza
AU - van Engeland, Manon
AU - Jacobs, Maarten A. J. M.
AU - van Wanrooij, Roy L. J.
AU - van der Peet, Donald L.
AU - Thorner, Aaron R.
AU - Verheul, Henk M. W.
AU - Thijssen, Victor L. J. L.
AU - Bass, Adam J.
AU - Derks, Sarah
N1 - Funding Information: We thank the Pathologisch Anatomisch Landelijk Geautomatiseerd Archief (PALGA) for their assistance in searching pretreatment biopsy specimen from the referring hospitals. SD is supported by the Dutch Cancer Society (VU2012‐5351), the Netherlands Organization for Scientific Research (NOW, 016.186.022), American Society of Clinical Oncology (YIA 2016) and Oncode Institute. AB receives funding from Bayer, Merck and Novartis. Funding Information: We thank the Pathologisch Anatomisch Landelijk Geautomatiseerd Archief (PALGA) for their assistance in searching pretreatment biopsy specimen from the referring hospitals. SD is supported by the Dutch Cancer Society (VU2012-5351), the Netherlands Organization for Scientific Research (NOW, 016.186.022), American Society of Clinical Oncology (YIA 2016) and Oncode Institute. AB receives funding from Bayer, Merck and Novartis. Publisher Copyright: © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - DNA sequencing
KW - chemoradiation
KW - gene methylation
KW - genetic biomarkers
KW - oesophageal cancer
KW - predictive markers
UR - http://www.scopus.com/inward/record.url?scp=85101279735&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/1878-0261.12907
DO - https://doi.org/10.1002/1878-0261.12907
M3 - Article
C2 - 33506581
SN - 1574-7891
VL - 15
SP - 901
EP - 914
JO - Molecular Oncology
JF - Molecular Oncology
IS - 4
ER -