L. Vanacker MD, D. Smeets PhD, A. Hoorens MD, PhD, E. Teugels PhD, R. Algaba MD, M.F. Dehou MD, A. De Becker MD, D. Lambrechts PhD, J. De Grève MD, PhD
We present the case of a 30-year-old male patient with a high grade neuroendocrine carcinoma and an adenocarcinoma developed in a tubulovillous adenoma of the colon, with diffuse liver metastasis. He underwent a right hemicolectomy and received four courses of postoperative chemotherapy with cisplatin and etoposide, followed by high dose chemotherapy with autologous stem cell support. After this treatment there was a complete biochemical and radiological remission. Now, 48 months after diagnosis the patient is alive and in unmaintained complete remission. The occurrence of a high grade neuroendocrine carcinoma in a low grade colon adenocarcinoma without any intermediate phenotypes was intriguing. Comparative exome sequencing of DNA from the malignant components revealed six somatic changes in cancer consensus genes. In both tumours, we detected mutations in APC and KRAS, as well as in BCL9 and FOXP1. Only in the neuroendocrine carcinoma component did we find a mutation in SMARCA4. All mutations were absent in germ-line DNA. The finding of several identical somatic mutations in both components in the subsequent exome sequencing supports a clonal relationship between the neuroendocrine carcinoma and the synchronous adenocarcinoma. We suggest that a mutation in SMARCA4A may be responsible for the abrupt transition to the aggressive neuroendocrine phenotype.