Early onset esophageal adenocarcinoma: a distinct molecular entity?
Anna M.J. van Nistelrooij1,2, Ronald van Marion1, PALGA-group3, Katharina Biermann1, Manon C.W. Spaander4, J. Jan B. van Lanschot2, Bas P.L. Wijnhoven2 and Winand N.M. Dinjens1
1 Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands
2 Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands
3 Members of the PALGA-group: I. van Lijnschoten, Pathology and Medical Microbiology, PAMM Institute, Eindhoven, The Netherlands. M. Hogenes, Laboratory of Pathology, Oost-Nederland, Hengelo, The Netherlands
4 Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands
Correspondence:
Winand N.M. Dinjens, email:
Keywords: esophageal adenocarcinoma, early onset cancer, molecular analysis
Received: December 26, 2015 Accepted: January 22, 2016 Published: February 01, 2016
Abstract
Esophageal adenocarcinoma (EAC) is typically diagnosed in elderly with a median age of 68 years. The incidence of EAC has been rising over the last decades, also among young adults. The aim of the study was to investigate whether early onset EAC is a distinct molecular entity.
To identify early onset EACs, the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA) was searched. Twenty-eight tumors of patients aged ≤40 years were selected and matched with 27 tumors of patients aged ≥68 years. DNA was isolated from surgically resected specimen and sequenced on the Ion Torrent Personal Genome Machine with the Ion AmpliSeq Cancer Panel.
No differences in mutational load between early onset and conventional EACs were observed (P=0.196). The most frequently mutated genes were TP53 (73%) and P16 (16%). Additional mutations in early onset EACs occurred exclusively in: APC, CDH1, CTNNB1, FGFR2, and STK11. In the conventional EACs additional mutations were exclusively identified in: ABL1, FBXW7, GNA11, GNAS, KRAS, MET, SMAD4, and VHL.
Additional mutations besides TP53 and P16 seem to occur in different genes related to cell fate pathways for early onset EACs, while the additional mutations in conventional EACs are related to survival pathways.
