Search results for "Exon"
showing 10 items of 437 documents
Abstract PD3-6: ConvertHER: Evolution of genomic alterations from primary to metastatic breast cancer
2015
Abstract Background: Changes in breast cancer receptor status over disease progression and treatment have been described to a point that could alter response to therapy. There is growing interest in delivering biomarker/genomically-based targeted therapies. We aimed to determine the concordance of genomic alterations between primary (P) and metastatic (M) breast cancer in a prospective collection study. Methods: Targeted capture and next-generation sequencing was performed on formalin-fixed paraffin-embedded (FFPE) samples, profiling 202 cancer relevant genes in 61 pairs (primary and corresponding recurrence/metastasis). Tumors were classified at baseline as [hormone receptor (HR)+/HER2-, H…
Second-line treatment in exon 11-mutated GIST patients: Imatinib dose escalation or sunitinib? Retrospective analysis of a multi-institutional experi…
2014
10515 Background: Data from metastatic GIST patients harbouring exon 11 mutation who received a second line treatment with sunitinib or imatinib dose escalation were retrospectively analysed to compare survival. Methods: 123 exon 11 mutated advanced GIST patients were included. All patients progressed on imatinib 400 mg/die and received, on discretion of physician, a second line treatment with either imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 weeks of or 37.5 mg/day continuous daily dose). The type of exon 11 mutation was recorded (deletion versus others) and correlated with survival and response according to RECIST or CHOI criteria Results: 79 patients (64%) received a seco…
Nm-23-H1 expression does not predict clinical survival in colorectal cancer patients
2003
The gene Nm23, which encodes for a nucleoside diphosphate kinase, has been defined as a metastasis-suppressor gene because of the inverse correlation between its expression and the metastatic capacity of the tumor cells. For colorectal cancer, however, the findings are equivocal. The aim of our study was to assess, in 160 patients undergoing surgery for colorectal cancer (CRC), the expression of the Nm23-H1 protein and to evaluate its possible associations with traditional clinicopathologic variables, with DNA-ploidy and proliferative activity (S-phase fraction, SPF), and with disease-free and overall survival of patients. Nm23-H1 expressions were evaluated on paraffin-embedded tissue by im…
Strong founder effects in BRCA1 mutation carrier breast cancer patients from Latvia
1999
Germ-line mutations of the BRCA1 gene account for approximately half of the cases of hereditary breast/ovarian cancers. We have screened index patients from 15 breast cancer families and 8 sporadic breast cancer patients from Latvia for mutations in all coding exons of the BRCA1 gene, using combined Heteroduplex Analysis/SSCP followed by direct sequencing of the variants. BRCA1 germ-line mutations proved to be frequent in Latvian breast cancer patients, also in moderate-risk families and sporadic patients. Out of 23 cases a total of 8 patients (35%) exhibited three different mutations (5382insC, C61G, 4153delA). Interestingly, these three recurrent mutations accounted for all mutations in o…
LungBEAM: A prospective multicenter study to monitor stage IV NSCLC patients with EGFR mutations using BEAMing technology
2021
Abstract Objectives The aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non‐small cell lung cancer (NSCLC) patients treated with first‐ or second‐generation EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival. Methods Stage IV NSCLC patients with locally confirmed EGFR‐TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to…
Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic …
2015
Abstract Purpose: We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective–retrospective analysis of a randomized, multicenter phase III study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183). Experimental Design: Outcomes were from the study's primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) we…
The prevalent KRAS exon 2 c.35 G > A mutation in metastatic colorectal cancer patients: a biomarker of worse prognosis and potential benefit of bevac…
2015
Bevacizumab-containing chemotherapy differently predict increased efficacy in KRAS exon 2 mutant and wild-type metastatic colorectal cancer (MCRC) patients. Mutant compared to wild-type status did not significantly affect progression-free survival (PFS) and overall survival (OS) in patients fit for first line bevacizumab-containing FIr-B/FOx regimen, and after progression. In patients unfit for intensive regimens, mutant status significantly affected PFS, while not OS. Codon 12 KRAS mutations differentially affect GTPase function, and confer worse clinical behaviour. Prognostic relevance of the prevalent c.35 G. >. A KRAS mutation was retrospectively evaluated. Fit c.35 G. >. A mutant patie…
Novel P53 mutations detected by FAMA in colorectal cancers
2006
Background The aim of the study was to identify p53 gene mutations by FAMA (fluorescence-assisted mismatch analysis) in colorectal cancers. Patients and methods Analytical scanning of the p53 gene (exons 5–9) was performed in colon cancer samples from 44 consecutive patients by FAMA. FAMA is a semiautomatic scanning approach based on the chemical cleavage of the mismatch in fluorescently labeled heteroduplex DNA, obtained from the combination of a normal and a mutated allele. FAMA has already shown optimal levels of diagnostic accuracy and sensitivity in detecting gene mutations (nucleotide substitutions, insertions/deletions) both at the germline and somatic level. The peculiar feature of …
Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
2006
Item does not contain fulltext BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified ac…
Cloning, chromosomal characterization and mapping of the NAD-dependent histone deacetylases gene sirtuin 1
2006
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, which belongs to the silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs). The yeast Sir2 protein and its mammalian derivatives play a central role in epigenetic gene silencing, DNA repair and recombination, cell-cycle, microtubule organization, and in the regulation of aging. We have isolated and characterized the human Sirt1 genomic sequence, which spans a region of 33,660 bp and which has one single genomic locus. Determination of the exon-intron splice junctions established that SIRT1 is encoded by 9 exons ranging in size from 80 bp (exon 6) to 2,120 bp (exon 9). Charac…