Reference Detail

Ref Type

Journal Article

PMID

(23917401)

Authors

Frattini V, Trifonov V, Chan JM, Castano A, Lia M, Abate F, Keir ST, Ji AX, Zoppoli P, Niola F, Danussi C, Dolgalev I, Porrati P, Pellegatta S, Heguy A, Gupta G, Pisapia DJ, Canoll P, Bruce JN, McLendon RE, Yan H, Aldape K, Finocchiaro G, Mikkelsen T, Prive GG, Bigner DD, Lasorella A, Rabadan R, Iavarone A

Title

The integrated landscape of driver genomic alterations in glioblastoma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Nature genetics	45	10	2013 Oct	1141-9	Nat Genet

URL

Abstract Text

Glioblastoma is one of the most challenging forms of cancer to treat. Here we describe a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma. We found mutations with loss of heterozygosity in LZTR1, encoding an adaptor of CUL3-containing E3 ligase complexes. Mutations and deletions disrupt LZTR1 function, which restrains the self renewal and growth of glioma spheres that retain stem cell features. Loss-of-function mutations in CTNND2 target a neural-specific gene and are associated with the transformation of glioma cells along the very aggressive mesenchymal phenotype. We also report recurrent translocations that fuse the coding sequence of EGFR to several partners, with EGFR-SEPT14 being the most frequent functional gene fusion in human glioblastoma. EGFR-SEPT14 fusions activate STAT3 signaling and confer mitogen independence and sensitivity to EGFR inhibition. These results provide insights into the pathogenesis of glioblastoma and highlight new targets for therapeutic intervention.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description
ATRX	Q1843H	missense	unknown	ATRX Q1843H does not lie within any known functional domains of the Atrx protein (UniProt.org). Q1843H has been identified in sequencing studies (PMID: 23917401), but has not been biochemically characterized and therefore, its effect on Atrx protein function is unknown (PubMed, Mar 2024).
CHEK1	K232N	missense	unknown	CHEK1 K232N lies within the protein kinase domain of the Chek1 protein (UniProt.org). K232N has been identified in sequencing studies (PMID: 23917401), but has not been biochemically characterized and therefore, its effect on Chek1 protein function is unknown (PubMed, Oct 2023).
CHEK1	R160H	missense	unknown	CHEK1 R160H lies within the protein kinase domain of the Chek1 protein (UniProt.org). R160H has been identified in the scientific literature (PMID: 23917401, PMID: 26674132, PMID: 34789479), but has not been biochemically characterized and therefore, its effect on Chek1 protein function is unknown (PubMed, Oct 2023).
PIK3CA	K111R	missense	unknown	PIK3CA K111R does not lie within any known functional domains of the Pik3ca protein (UniProt.org). K111R has been identified in sequencing studies (PMID: 28027320, PMID: 27641744, PMID: 23917401), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024).
PTEN	T277I	missense	unknown	PTEN T277I lies within the C2 tensin-type domain of the Pten protein (UniProt.org). T277I has been identified in sequencing studies (PMID: 23917401, PMID: 32351019, PMID: 35052351), but has not been biochemically characterized and therefore, its effect on Pten protein function is unknown (PubMed, Dec 2023).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References