Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients.
Nat Commun
; 10(1): 3722, 2019 08 19.
Article
in En
| MEDLINE
| ID: mdl-31427573
ABSTRACT
Colorectal cancer (CRC) is increasingly appreciated as a heterogeneous disease, with factors such as microsatellite instability (MSI), cancer subsite within the colon versus rectum, and age of diagnosis associated with specific disease course and therapeutic response. Activating oncogenic mutations in KRAS and NRAS are common in CRC, driving tumor progression and influencing efficacy of both cytotoxic and targeted therapies. The RAS mutational spectrum differs substantially between tumors arising from distinct tissues. Structure-function analysis of relatively common somatic RAS mutations in G12, Q61, and other codons is characterized by differing potency and modes of action. Here we show the mutational profile of KRAS, NRAS, and the less common HRAS in 13,336 CRC tumors, comparing the frequency of specific mutations based on age of diagnosis, MSI status, and colon versus rectum subsite. We identify mutation hotspots, and unexpected differences in mutation spectrum, based on these clinical parameters.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rectal Neoplasms
/
Genetic Variation
/
Proto-Oncogene Proteins p21(ras)
/
Colonic Neoplasms
/
GTP Phosphohydrolases
/
Membrane Proteins
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2019
Type:
Article
Affiliation country:
United States