Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma.
Cancer Cell
; 20(6): 810-7, 2011 Dec 13.
Article
in En
| MEDLINE
| ID: mdl-22137795
ABSTRACT
Tumor heterogeneity has been implicated in tumor growth and progression as well as resistance to therapy. We present an example of genetic heterogeneity in human malignant brain tumors in which multiple closely related driver genes are amplified and activated simultaneously in adjacent intermingled cells. We have observed up to three different receptor tyrosine kinases (EGFR, MET, PDGFRA) amplified in single tumors in different cells in a mutually exclusive fashion. Each subpopulation was actively dividing, and the genetic changes resulted in protein production, and coexisting subpopulations shared common early genetic mutations indicating their derivation from a single precursor cell. The stable coexistence of different clones within the same tumor will have important clinical implications for tumor resistance to targeted therapies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Glioblastoma
/
Proto-Oncogene Proteins c-met
/
Receptor, Platelet-Derived Growth Factor alpha
/
ErbB Receptors
/
Mosaicism
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Cancer Cell
Journal subject:
NEOPLASIAS
Year:
2011
Type:
Article
Affiliation country:
United States