Thor Halfdanarson, Professor of Oncology at Mayo Clinic School of Medicine, shared on X:
“The poorly differentiated neuroendocrine carcinomas of the colon and rectum are a major clinical challenge and the mixed tumors, the mixed neuroendocrine–non-neuroendocrine neoplasms (MiNEN) even more so. This excellent study explored the origin and evolution of colorectal MiNENs using specimens from 10 subjects in the NORDIC NEC 2 study.
Some key findings:
- All ten cases revealed a common trunk of shared somatic mutations, including well-known colorectal cancer driver mutations such as BRAF, KRAS, APC, and TP53
- In all cases, a single branching point separated the AC and NEC components
- Private AC and NEC mutations generally had low variant allele frequencies, indicating that most AC and NEC cells were genetically similar.
- Shared mutations indicate a common clonal origin, underscoring the role of established colorectal driver mutations in the early development of these tumors, while the mechanisms underlying NEC differentiation remain poorly understood.
If there is one thing I have learned by experience, it is that conventional NEC therapy, such as platinum and etoposide is very inadequate for colorectal NECs with low response rates and short control. Perhaps the genomics explain that… Also, conventional colorectal adenocarcinoma therapy, especially if including irinotecan, may work better but well-designed trials are badly needed to test that hypothesis.”
Title: Origin and evolution of colorectal mixed neuroendocrine–non-neuroendocrine neoplasms (MiNEN)
Authors: Siren Morken, Halfdan Sorbye, Wei Deng, Hatice Toprak Dogramaci, Andreas Venizelos, Lene Weber Vestermark, Per Pfeiffer, Christian Kersten, Aurel Perren, Stian Knappskog.
You can also read ‘Fight Colorectal Cancer Welcomes 3 New Organizations to the Colorectal Cancer Care Initiative‘
