Mixed adenoneuroendocrine carcinoma of the colon: molecular pathogenesis and treatment

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 cisplati...

Full description

Saved in:
Bibliographic Details
Published in:Anticancer research 2014-10, Vol.34 (10), p.5517-5521
Main Authors: Vanacker, Leen, Smeets, Dominiek, Hoorens, Anne, Teugels, Erik, Algaba, Roberto, Dehou, Marie Françoise, De Becker, Ann, Lambrechts, Diether, De Greve, Jacques
Format: Article
Language:English
Subjects:
Adult
Biopsy
Carcinoma, Neuroendocrine - diagnosis
Carcinoma, Neuroendocrine - genetics
Carcinoma, Neuroendocrine - therapy
Colonic Neoplasms - diagnosis
Colonic Neoplasms - genetics
Colonic Neoplasms - therapy
Humans
Male
Mutation
Neoplasm Grading
Neoplasm Staging
Treatment Outcome
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1791-7530