Differences in the molecular organisation of tumours along the colon are linked to interactions within the tumour ecosystem.
Biochim Biophys Acta Mol Basis Dis
; 1870(7): 167311, 2024 10.
Article
in En
| MEDLINE
| ID: mdl-38909851
ABSTRACT
Tumours exhibit significant heterogeneity in their molecular profiles across patients, largely influenced by the tissue of origin, where certain driver gene mutations are predominantly associated with specific cancer types. Here, we unveil an additional layer of complexity some cancer types display anatomic location-specific mutation profiles akin to tissue-specificity. To better understand this phenomenon, we concentrate on colon cancer. While prior studies have noted changes of the frequency of molecular alterations along the colon, the underlying reasons and whether those changes occur rather gradual or are distinct between the left and right colon, remain unclear. Developing and leveraging stringent statistical models on molecular data from 522 colorectal tumours from The Cancer Genome Atlas, we reveal disparities in molecular properties between the left and right colon affecting many genes. Interestingly, alterations in genes responsive to environmental cues and properties of the tumour ecosystem, including metabolites which we quantify in a cohort of 27 colorectal cancer patients, exhibit continuous trends along the colon. Employing network methodologies, we uncover close interactions between metabolites and genes, including drivers of colon cancer, showing continuous abundance or alteration profiles. This underscores how anatomic biases in the composition and interactions within the tumour ecosystem help explaining gradients of carcinogenesis along the colon.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colon
/
Mutation
Limits:
Humans
Language:
En
Journal:
Biochim Biophys Acta Mol Basis Dis
/
Biochim. biophys. acta, Mol. basis dis
/
Biochimica et biophysica acta. Molecular basis of disease
Year:
2024
Type:
Article
Affiliation country:
Italy