Search results for "MUTATION"

What are the Cancer Risks in BRCA Carriers Apart from Those Regarding the Breast and the Ovary?

2012

Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose to familial breast and/or ovarian cancer. The lifetime risk of members of families with genetic predisposition depends on the mutations of susceptibility genes. BRCA1 mutations seem to confer the highest risk of developing neoplastic diseases. Apart from breast and ovarian cancer mutations in BRCA, related pathways are supposed to confer a smaller risk for additional cancers (colon, melanoma, pancreas, lymphoma, prostate, liver). All these tumors have an inherited component not necessarily associated with genetic susceptibility to BRCA genes. To date he main focus of this review has been argued still with difficulty…

The role of second and third line tyrosine kinase inhibitor monotherapy in EGFR wild-type (and unknown mutational status) advanced non-small-cell lun…

2015

<i>BRAF</i> Mutation Testing in Lynch Syndrome Diagnostics: Performance and Efficiency According to Patient's Age

2019

Background: BRAF V600E mutations are reportedly associated with sporadic microsatellite-unstable (MSI) colorectal cancer (CRC), while rarely detected in CRCs of Lynch syndrome (LS) patients. Therefore, current international diagnostic guidelines recommend somatic BRAF mutation testing in MLH1-deficient MSI CRC patients to exclude LS. As sporadic BRAF- mutant MSI CRC is a disease of the elderly, while LS-associated CRC usually occurs at younger age, we hypothesized that the efficacy of BRAF testing in LS diagnostics may be age-dependent. Methods: We systematically compared the prevalence of BRAF mutations in LS-associated CRCs and MSI CRCs from population-based cohorts in different age group…

Mosaic Study: Actualization of Overall Survival (Os) with 10 Years Follow Up and Evaluation of Braf. By Gercor and Mosaic Investigators

2014

ABSTRACT Aim: The MOSAIC study (Andre T, N Engl J Med, 2004) has demonstrated in patients with stage II/III resected colon cancer (CC) a benefit of oxaliplatin added to 5FU and LV (LV5FU) in 3-year disease-free survival (DFS) and in overal survival (OS). LV5FU and oxaliplatin (FOLFOX4) has also shown a benefit in deficient MisMatch Repair (dMMR) CC pts (Flejou JF, J Clin Oncol 31: 2013;suppl; abstr 3524). We report here 1) Results of MOSAIC after 10 year follow-up, and 2) results in the BRAF evaluable population. Methods: Of the 2246 patients included in the MOSAIC study (whole population), the actualization of survival data was done with 10 yrs follow up. Formalin-fixed, paraffin-embedded …

Hereditary ovarian cancer.

2008

Apoptosis is a form of cell death that permits the removal of damaged, senescent or unwanted cells in multicellular organisms, without damage to the cellular microenvironment. Defective apoptosis represents a major causative factor in the development and progression of cancer. The majority of chemotherapeutic agents, as well as radiation, utilize the apoptotic pathway to induce cancer cell death. Resistance to standard chemotherapeutic strategies also seems to be due to alterations in the apoptotic pathway of cancer cells. Recent knowledge on apoptosis has provided the basis for novel targeted therapies that exploit apoptosis to treat cancer. These new target include those acting in the ext…

Outcome of patients with CML treated with dasatinib or nilotinib after failure of second prior TKIs.

2010

Abstract Abstract 2294 Background. The TKIs Nilotinib and Dasatinib offer additional therapeutic options for patients with CML who are resistant or intolerant to Imatinib. These agents, active against the majority of Imatinib resistant BCR-ABL mutated clones, have a different pattern of kinase target selectivity, pharmacokinetics parameters, cell uptake, efflux properties and adverse events profiles. Preliminary results suggest that some patients may respond to a second TKI used as third line therapy, but little is known about the long term benefit of such an approach.Aim of this collaborative Italian study was to verify the response (rate and duration) and the clinical outcome in patients …

KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.

2009

Background: Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling. Objective/Methods: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data. Results/conclusions: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be consi…

Targeted next generation sequencing of breast implant-associated anaplastic large cell lymphoma reveals mutations in JAK/STAT signalling pathway gene…

2016

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention

2014

// Nicole M. Davis 1 , Melissa Sokolosky 1 , Kristin Stadelman 1 , Stephen L. Abrams 1 , Massimo Libra 2 , Saverio Candido 2 , Ferdinando Nicoletti 2 , Jerry Polesel 3 , Roberta Maestro 4 , Antonino D’Assoro 5 , Lyudmyla Drobot 6 , Dariusz Rakus 7 , Agnieszka Gizak 7 , Piotr Laidler 8 , Joanna Dulinska-Litewka 8 , Joerg Basecke 9 , Sanja Mijatovic 10 , Danijela Maksimovic-Ivanic 10 , Giuseppe Montalto 11,12 , Melchiorre Cervello 12 , Timothy L. Fitzgerald 13 , Zoya N. Demidenko 14 , Alberto M. Martelli 15 , Lucio Cocco 15 , Linda S. Steelman 1 and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC 27858 USA 2 …

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…