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Mouliere F.,Institute Of Recherche En Cancerologie Of Montpellier | Mouliere F.,French Institute of Health and Medical Research | Mouliere F.,Montpellier University | Mouliere F.,Institute regional du Cancer Montpellier | And 30 more authors.
Translational Oncology | Year: 2013

We used a novel method based on allele-specific quantitative polymerase chain reaction (Intplex) for the analysis of circulating cell-free DNA (ccfDNA) to compare total ccfDNA and KRAS- or BRAF-mutated ccfDNA concentrations in blood samples from mice xenografted with the human SW620 colorectal cancer (CRC) cell line and from patients with CRC. Intplex enables single-copy detection of variant alleles down to a sensitivity of ≥0.005 mutant to wild-type ratio. The proportion of mutant allele corresponding to the percentage of tumor-derived ccfDNA was elevated in xenografted mice with KRAS homozygous mutation and varied highly from 0.13% to 68.7% in samples from mutationpositive CRC patients (n = 38). Mutant ccfDNA alleles were quantified in the plasma of every patient at stages II/III and IV with a mean of 8.4% (median, 8.4%) and 21.8% (median, 12.4%), respectively. Twelve of 38 (31.6%) and 5 of 38 (13.2%) samples showed a mutation load higher than 25%and 50%, respectively. This suggests that an important part of ccfDNA may originate from tumor cells. In addition, we observed that tumor-derived (mutant) ccfDNA was more fragmented than ccfDNA from normal tissues. This observation suggests that the form of tumor-derived and normal ccfDNA could differ. Our approach revealed that allelic dilution is much less pronounced than previously stated, considerably facilitating the noninvasive molecular analysis of tumors. © 2013 Neoplasia Press, Inc. All rights reserved.

Jacot W.,CRLC Val dAurelle Paul Lamarque | Lopez-Crapez E.,Laboratoire Of Biologie Specialisee Et Doncogenetique | Thezenas S.,CRLC Val dAurelle Paul Lamarque | Senal R.,Laboratoire Of Biologie Specialisee Et Doncogenetique | And 4 more authors.
Breast Cancer Research | Year: 2011

Introduction: Triple-negative breast cancers (TNBCs) are characterised by lack of expression of hormone receptors and epidermal growth factor receptor 2 (HER-2). As they frequently express epidermal growth factor receptors (EGFRs), anti-EGFR therapies are currently assessed for this breast cancer subtype as an alternative to treatments that target HER-2 or hormone receptors. Recently, EGFR-activating mutations have been reported in TNBC specimens in an East Asian population. Because variations in the frequency of EGFR-activating mutations in East Asians and other patients with lung cancer have been described, we evaluated the EGFR mutational profile in tumour samples from European patients with TNBC.Methods: We selected from a DNA tumour bank 229 DNA samples isolated from frozen, histologically proven and macrodissected invasive TNBC specimens from European patients. PCR and high-resolution melting (HRM) analyses were used to detect mutations in exons 19 and 21 of EGFR. The results were then confirmed by bidirectional sequencing of all samples.Results: HRM analysis allowed the detection of three EGFR exon 21 mutations, but no exon 19 mutations. There was 100% concordance between the HRM and sequencing results. The three patients with EGFR exon 21 abnormal HRM profiles harboured the rare R836R SNP, but no EGFR-activating mutation was identified.Conclusions: This study highlights variations in the prevalence of EGFR mutations in TNBC. These variations have crucial implications for the design of clinical trials involving anti-EGFR treatments in TNBC and for identifying the potential target population. © 2012 Jacot et al.; licensee BioMed Central Ltd.

PubMed | ICM Val dAurelle and Laboratoire Of Biologie Specialisee Et Doncogenetique
Type: Journal Article | Journal: Bulletin du cancer | Year: 2014

There is a recent increase in interest of vitamin D and breast cancer, facing the number of publications on the subject. This increase have several reasons, on the one hand, vitamin D deficiency is more and more prevalent and, on the other hand, there are new data that highlights the extra-bone effects of vitamin D, especially in breast cancer, the vitamin D is involved in the breast cancer risk factor, the prognosis, and the interaction with breast cancer treatments. This combination between vitamin D deficiency and breast cancer is extremely usual, and combined with all cancer clinical parameters: the incidence, the tumour biology, the clinical presentation, the prognosis, and the antineoplastic treatment tolerance. This vitamin D deficiency is increased after adjuvant cancer treatments. And yet, this problem increases bone metabolism disruptions in breast cancer patients, inducing osteoporotic risk at long time, even though this population is curable. This problem is therefore serious in the adjuvant breast cancer treatment. Unfortunately, in this population, the current recommendations are clearly insufficient, and the current randomized clinical trial results would contribute to define the best way to correct the vitamin D deficiency, quickly and secure.

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