scholarly journals Gene Mutation Analysis in EGFR Wild Type NSCLC Responsive to Erlotinib: Are There Features to Guide Patient Selection?

2014 ◽  
Vol 16 (1) ◽  
pp. 747-757 ◽  
Author(s):  
Paola Ulivi ◽  
Angelo Delmonte ◽  
Elisa Chiadini ◽  
Daniele Calistri ◽  
Maximilian Papi ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Mutation Analysis ◽  
Patient Selection ◽  
Wild Type ◽  
Gene Mutation Analysis

Somatic G17V Rhoa Mutation Specifies Angioimmunoblastic T-Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 815-815
Author(s):  
Mamiko Sakata-Yanagimoto ◽  
Terukazu Enami ◽  
Kenichi Yoshida ◽  
Yuichi Shiraishi ◽  
Ryohei Ishii ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Gene Mutation ◽  
Mutation Analysis ◽  
Cell Lymphoma ◽  
Molecular Pathogenesis ◽  
T Cell Lymphoma ◽  
Wild Type ◽  
Angioimmunoblastic T Cell Lymphoma ◽  
Gene Mutation Analysis

Abstract Background Angioimmunoblastic T-cell lymphoma (AITL) is a distinct subtype of peripheral T-cell lymphoma (PTCL) characterized by generalized lymphadenopathy, hyperglobulinemia, and autoimmune-like manifestations. Frequent mutations in TET2, IDH2, and DNMT3A have been described in AITL, which are commonly found in myeloid malignancies. However, the molecular pathogenesis specific to AITL is still unknown. Methods To clarify the molecular pathogenesis of AITL, we performed comprehensive gene-mutation analysis. Somatic mutations in 3 AITL and 3 PTCL-NOS specimens were explored using whole-exome sequencing (WES). Targeted resequencing for genes identified by WES was also performed in a cohort of 157 patients with AITL/PTCL-NOS. Results We identified a novel recurrent mutation in RHOA (c.G50T/p.G17V) in 3 AITL and one PTCL-NOS samples by WES. Validation in an extended cohort revealed an extremely high frequency of the identical G17V RHOA mutation in AITL (50/72 [69.4%]), together with mutations in TET2 (39/47 [83.0%]), IDH2 (14/47 [29.8%]), and DNMT3A(12/47 [25.5%]). The G17V RHOA mutation was also found in PTCL-NOS samples at a lower frequency (14/85 [16.5%]), especially in those harboring AITL features (PTCL-NOS with AITL features vs PTCL-NOS w/o AITL features: 13/21 [61.9%] vs 0/38 [0%]). Remarkably, mutations in RHOA, TET2, and IDH2 showed striking correlations. All RHOA-mutated samples were accompanied by TET2 mutations. IDH2 mutations were confined to the samples having simultaneous mutations of RHOA and TET2. Mutations in DNMT3A largely overlapped to TET2 mutations, but its correlation with RHOA or IDH2 mutations was much less clear. TET2 mutations showed a consistently higher allelic burden than RHOA mutations. Gene-mutation analysis of tumor cells and infiltrated cells demonstrated that the G17V RHOA mutation specifically existed in tumor cells, but not in non-tumor cells, while TET2 mutations were identified both in tumor and non-tumor cells. RHOA encodes a small GTPase, which operates as a molecular switch that regulates a wide variety of biological processes through cycling between an active (GTP-bound) and an inactive (GDP-bound) state. We demonstrated that the G17V RHOA mutant did not bind GTP and also inhibited GTP-binding of the wild-type RHOA protein. Accordingly, unlike wild-type RHOA, the G17V mutant was not able to activate transcription from the serum response factor-responsive element (SRF-RE). Conclusions Our data suggests that combination of preceding mutations in TET2 and subsequent tumor-specific G17V RHOA mutation determines distinct disease properties of AITL. Disclosures: No relevant conflicts of interest to declare.

Genetic counselling and gene mutation analysis in familial adenomatous polyposis in Western Australia

1995 ◽  
Vol 162 (9) ◽  
pp. 464-467 ◽  
Author(s):  
Ian R Walpole ◽  
Jack Goldblatt ◽  
Deborah A Kool ◽  
Ted Edkins ◽  
Rhona Creegan ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Gene Mutation ◽  
Genetic Counselling ◽  
Mutation Analysis ◽  
Western Australia ◽  
Adenomatous Polyposis ◽  
Gene Mutation Analysis

TGFBI Gene Mutation Analysis in Families with Hereditary Corneal Dystrophies from Ukraine

2004 ◽  
Vol 218 (6) ◽  
pp. 411-414 ◽  
Author(s):  
V.M. Pampukha ◽  
G.I. Drozhyna ◽  
L.A. Livshits
Keyword(s):  
Gene Mutation ◽  
Mutation Analysis ◽  
Corneal Dystrophies ◽  
Tgfbi Gene ◽  
Gene Mutation Analysis

Gene Mutation Analysis in Determining Late Recurrence of Adenocarcinoma of the Lung

2015 ◽  
Vol 100 (2) ◽  
pp. 711-713
Author(s):  
Nobuyuki Kondo ◽  
Teruhisa Takuwa ◽  
Masaki Hashimoto ◽  
Kazue Yoneda ◽  
Seiji Matsumoto ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Mutation Analysis ◽  
Late Recurrence ◽  
Adenocarcinoma Of The Lung ◽  
Gene Mutation Analysis
Sign in / Sign up

Export Citation Format

Share Document