title: Mixed adenoneuroendocrine carcinoma of the colon: molecular pathogenesis and treatment.
abstract: We report a case of a mixed adenoneuroendocrine carcinoma developed in a colorectal adenocarcinoma with lymph node and liver metastases exclusively emanating from the neuroendocrine carcinoma component. The patient underwent right hemicolectomy and postoperatively received chemotherapy with cisplatin and etoposide and subsequent high-dose induction chemotherapy, followed by autologous stem cell transplantation. Following this treatment, there was a complete remission. Currently, thirty months after treatment, the patient is in unmaintained complete remission. Comparative exome sequencing of germline DNA and DNA from the two separate malignant components revealed six somatic changes in cancer consensus genes. Both components shared somatic mutations in Adenomatous polyposis coli (APC), Kirsten rat sarcoma viral oncogene homolog (KRAS), B-cell CLL/lymphoma 9 (BCL9) and Forkhead Box P1 (FOXP1) genes. Mutation in SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) was only found in the neuroendocrine carcinoma component. The finding of several identical somatic mutations in both components supports a clonal relationship between the neuroendocrine carcinoma and the adenocarcinoma. We suggest that a mutation in SMARCA4 could be responsible for the transformation of the adenocarcinoma component into the neuroendocrine phenotype.
authors.affiliation: Laboratory of Molecular Oncology, Department of Medical Oncology, Brussels, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Vanacker
authors.affiliation: Vesalius Research Cancer, Flemish Institute for Biotechnology, Leuven, Belgium Laboratory for Translational Genetics, Department of Oncology, Catholic University Leuven, Belgium.
authors.forename: Dominiek
authors.initials: D
authors.lastname: Smeets
authors.affiliation: Department of Pathology, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Hoorens
authors.affiliation: Laboratory of Molecular Oncology, Department of Medical Oncology, Brussels, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Teugels
authors.affiliation: Department of Surgery and Pathology, Iris Hospitals South Campus Joseph Bracops, Brussels, Belgium.
authors.forename: Roberto
authors.initials: R
authors.lastname: Algaba
authors.affiliation: Department of Surgery and Pathology, Iris Hospitals South Campus Joseph Bracops, Brussels, Belgium.
authors.forename: Marie Françoise
authors.initials: MF
authors.lastname: Dehou
authors.affiliation: Department of Clinical Hematology, Brussels, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: De Becker
authors.affiliation: Vesalius Research Cancer, Flemish Institute for Biotechnology, Leuven, Belgium Laboratory for Translational Genetics, Department of Oncology, Catholic University Leuven, Belgium.
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.affiliation: Laboratory of Molecular Oncology, Department of Medical Oncology, Brussels, Belgium jacques.degreve@uzbrussel.be.
authors.forename: Jacques
authors.initials: J
authors.lastname: De Greve
mesh_terms: D000328:Adult; D001706:Biopsy; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D008297:Male; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016896:Treatment Outcome
keywords: MANEC; Mixed adenoneuroendocrine carcinoma; SMARCA4; autologous stem cell transplantation; colorectal adenocarcinoma; exome sequencing; high-dose chemotherapy; long-term survival