Detection of Colorectal Cancer and Advanced Adenoma by Liquid Biopsy (Decalib Study): The ddPCR Challenge.

Background: In most countries, participation in colorectal cancer (CRC) screening programs with the immunological fecal occult blood test (iFOBT) is low. Mutations of RAS and BRAF occur early in colorectal carcinogenesis and "liquid biopsy" allows detection of mutated circulating tumor DNA (ctDNA). This prospective study aims to evaluate the performance of RAS and BRAF-mutated ctDNA in detecting CRC and advanced adenomas (AA).

Pathological and Molecular Characteristics of Colorectal Cancer with Brain Metastases.

Colorectal cancers (CRC) with brain metastases (BM) are scarcely described. The main objective of this study was to determine the molecular profile of CRC with BM. We included 82 CRC patients with BM.

Association between clinicopathological characteristics and RAS mutation in colorectal cancer.

In colorectal cancer, KRAS (exons 2, 3, and 4) and NRAS (exons 2, 3, and 4) mutations are associated with resistance to antiepidermal growth factor receptor monoclonal antibodies, and BRAF mutation is a molecular marker of poor prognosis. KRAS exon 2 and BRAF-mutated colorectal cancers have well-known distinct clinicopathological characteristics. Comparison of tumors with different RAS status (exons 2, 3, and 4 of KRAS and NRAS) based on their clinicopathological characteristics has never been established.

Crizotinib targets in glioblastoma stem cells.

Glioblastoma stem cells (GSCs) are believed to be involved in the mechanisms of tumor resistance, therapeutic failures, and recurrences after conventional glioblastoma therapy. Therefore, elimination of GSCs might be a prerequisite for the development of successful therapeutic strategies. ALK, ROS1, and MET are targeted by Crizotinib, a tyrosine kinase inhibitor which has been approved for treatment of ALK-rearranged non-small-cell lung cancer.

Development of pyrosequencing methods for the rapid detection of RAS mutations in clinical samples.

In advanced colorectal carcinoma (CRC) patients, extended RAS mutations testing (KRAS exons 2 to 4 and NRAS exons 2 to 4) is a prerequisite for patient stratification to anti-EGFr therapy. Accurately distinguishing mutant patients from potential responders has a clinically critical impact, and thus effective and low cost methods are needed for identification of the mutation status. We have developed quantitative pyrosequencing assays for sensitive and rapid detection of mutant RAS alleles in formalin-fixed, paraffin-embedded tissues.

EGFR, KRAS, BRAF, and HER-2 molecular status in brain metastases from 77 NSCLC patients.

The aim of this study was to determine the frequency of EGFR, KRAS, BRAF, and HER-2 mutations in brain metastases from non-small cell lung carcinomas (BM-NSCLC). A total of 77 samples of BM-NSCLC were included and 19 samples of BM from breast, kidney, and colorectal tumors were also studied as controls. These samples were collected from patients followed between 2008 and 2011 at Poitiers and Nice University Hospitals in France.

Epidermal growth factor receptor (EGFR) and KRAS mutations during chemotherapy plus anti-EGFR monoclonal antibody treatment in metastatic colorectal cancer.

It is now well established that metastatic colorectal cancer patients without KRAS mutation (codon 12) benefit from treatment with an epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb). Recently, EFGR and KRAS mutations have been shown to exist in patients who developed resistance to anti-EGFR mAb. We analyzed KRAS, BRAF V600E and EGFR S492R mutations in 37 post-anti-EGFR mAb tumor samples from 23 patients treated with chemotherapy plus anti-EGFR mAb.

O6-Methylguanine-methyltransferase (MGMT) promoter methylation status in glioma stem-like cells is correlated to temozolomide sensitivity under differentiation-promoting conditions.

Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance.

STAT3 is essential for the maintenance of neurosphere-initiating tumor cells in patients with glioblastomas: a potential for targeted therapy?

Glioblastoma (GBM), the highest-grade form of gliomas, is the most frequent and the most aggressive. Recently, a subpopulation of cells with stem cells characteristics, commonly named "tumor-initiating stem cells" (TISCs) or "cancer stem cells" (CSCs) were identified in GBM. These cells were shown to be highly resistant to chemotherapeutic drugs and to ionizing radiations.

Neutrophil gelatinase-associated lipocalin expression in chronic myeloid leukemia.

The murine equivalent of neutrophil gelatinase-associated lipocalin (NGAL) was previously found to be increased by BCR-ABL expression in murine models of chronic myeloid leukemia (CML). Our study evaluates, in CML patients at various clinical stages, the levels of NGAL mRNA in blood samples and protein in sera. A highly significant increase of mRNA expression and protein secretion was shown in patients at diagnosis.

Gene expression profiling in anaplastic large cell lymphoma and Hodgkin's disease.

Recent efforts have been made to isolate molecular targets that could explain different outcome between histological subtypes of lymphomas and to understand the molecular mechanisms underlying oncogenic events. Using the SSH technique, we compared the transcriptome of 2 cases of ALK+ and ALK- anaplastic large cell lymphoma (ALCL) and of 2 cases of classical Hodgkin's lymphoma (cHL) with opposite behavior. Regarding ALCL, we showed that ALK-positive tumors overexpressed genes involved in different signaling pathways such as activation or signaling of T-cells, regulation of apoptosis, phospholipase Cgamma and phosphatidyl inositol-3 Kinase.

Comparison of M-FISH and conventional cytogenetic analysis in accelerated and acute phases of CML.

FISH and multicolor FISH (M-FISH) techniques have greatly enhanced the resolution of conventional cytogenetic analysis, thus enabling the identification of novel regions of rearrangement in hematological malignancies. We report on the analysis of cells from 24 chronic myelogenous leukemia (CML) patients, in either accelerated phase (14 cases) or blast crisis (10 cases) aimed at searching for previously unidentified additional abnormalities related to disease evolution. Indeed, in 6 of 24 cases (25%) M-FISH allowed a more precise description of chromosomal aberrations, the finding of cryptic rearrangements, characterization of markers, identification of additional material and a better interpretation of complex aberrations.

Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor alpha receptor: a new clinical target for STI571/Glivec.

Two cases of atypical chronic myeloid leukaemia (CML) carrying the t(4;22)(q12;q11) translocation involving the breakpoint cluster region (BCR) and platelet-derived growth factor alpha receptor (PDGFRA) genes have been recently characterized. We report a third case of atypical CML with the same translocation but with a distinct breakpoint fusing BCR exon 1 with PDGFRA exon 13. The patient had a clinical presentation of CML with progressive transformation in B-cell acute lymphoblastic leukaemia.

Isolation of differentially expressed genes in NPM-ALK-positive anaplastic large cell lymphoma.

In this study, we used subtractive suppression hybridization to compare gene expression between an ALK-positive anaplastic large cell lymphoma (ALCL)-derived cell line and a clinical case of ALK-negative ALCL. Construction and screening of a subtracted library resulted in the cloning of 29 cDNAs which were differentially expressed. Most of these clones corresponded to novel genes with unknown function (EST) or to genes implicated in the differentiation, activation or signalling of T cells such as Ran/TC4, interleukin 1-receptor, thymosin beta4, thymosin beta10, moesin and cytohesin-1.