Publications by authors named "V Duranton-Tanneur"

10 Publications

Molecular follow-up of first-line treatment by osimertinib in lung cancer: Importance of using appropriate tools for detecting EGFR resistance mutation C797S.

Cancer Genet 2021 Aug 10;256-257:158-161. Epub 2021 Jun 10.

Laboratory of Solid Tumor Genetics, University Hospital of Nice-Côte d'Azur University, Nice, France; Laboratory of Solid Tumor Genetics, Institute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR 7284/INSERM U1081, Nice, France. Electronic address:

The C797S mutation encoded by EGFR exon 20 is classically observed as a tertiary event in EGFR-mutant non-small-cell lung carcinoma (NSCLC) primarily treated by first generation tyrosine kinase inhibitors (TKI) and secondarily treated by third-generation TKI, such as osimertinib, if the EGFR-T790M resistance mutation is detected. Recently, significant prolonged progression free survival has been observed following first-line osimertinib, in EGFR-mutant NSLC. While mechanisms of molecular resistance to first-generation TKI have been well studied, little is known about resistance induced by primary third-generation TKI treatments. We report the case of a 65 year-old female treated by first-line osimertinib for a multimetastatic exon 19-EGFR-mutant NSCLC. EGFR-C797S resistance mutation and PIK3CA mutation were detected together with the remaining EGFR-exon 19 deletion. This observation provides insights of acquired resistance to first line-osimertinib. It also highlights the importance of making molecular platforms which perform routine EGFR testing in lung cancer aware of the kind of therapeutic protocols given to the patient. Indeed, for rapid results or low-costs procedures, some targeted methods specifically targeting T790M may be used at relapse and may overlook alterations such as C797S or PIK3CA mutations. Targeted next generation sequencing is therefore a recommended option.
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August 2021

[Detection of RAS genes mutation using the Cobas method in a private laboratory of pathology: Medical and economical study in comparison to a public platform of molecular biology of cancer].

Bull Cancer 2017 Jul - Aug;104(7-8):662-674. Epub 2017 Jul 5.

Laboratoire Médipath, pôle d'excellence Jean-Louis, 263, Via Nova, 83600 Fréjus, France.

In France, determination of the mutation status of RAS genes for predictive response to anti-EGFR targeted treatments is carried out by public platforms of molecular biology of cancer created by the French National Cancer Institute. This study aims to demonstrate the feasibility of these analyses by a private pathology laboratory (MEDIPATH) as per the requirements of accreditation. We retrospectively studied the mutation status of KRAS and NRAS genes in 163 cases of colorectal metastatic cancer using the Cobas technique. We compared our results to those prospectively obtained through pyrosequencing and allelic discrimination by the genetic laboratory of solid tumors at the Nice University Hospital (PACA-EST regional platform). The results of both series were identical: 98.7% positive correlation; negative correlation of 93.1%; overall correlation of 95.7% (Kappa=0.92). This study demonstrates the feasibility of molecular analysis in a private pathology laboratory. As this practice requires a high level of guarantee, its accreditation, according to the NF-EN-ISO15189 quality compliance French standard, is essential. Conducting molecular analysis in this context avoids the steps of routing the sample and the result between the pathology laboratory and the platform, which reduces the overall time of rendering the result. In conclusion, the transfer of some analysis from these platforms to private pathology laboratories would allow the platforms to be discharged from a part of routine testing and therefore concentrate their efforts to the development of new analyses constantly required to access personalized medicine.
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August 2017

Association of Oncogenic Mutations in Patients With Advanced Cutaneous Squamous Cell Carcinomas Treated With Cetuximab.

JAMA Dermatol 2017 Apr;153(4):291-298

Department of Dermatology, University Hospital of Nice, France.

Importance: Cetuximab was recently proposed for advanced cutaneous squamous cell carcinomas (cSCC); however, its efficacy is inconsistent and identification of predictive biomarkers for response is necessary.

Objective: To search for somatic mutations of the HRAS, KRAS, NRAS, BRAF, and EGFR genes in patients with advanced cSCC treated with cetuximab; and to investigate the efficacy and tolerance of cetuximab according to these mutations.

Design, Setting, And Participants: A multicentric and retrospective study of 31 patients (22 men, 9 women) with histologically confirmed advanced cSCC carried out in 1 department of dermatology and 2 departments of medical oncology in France between January 2008 and December 2014. The median age of participants was 86 years (range, 48-96 years).

Interventions: Mutational status was determined by pyrosequencing method, allelic discrimination, or Sanger sequencing. Patients were treated by single-agent cetuximab.

Main Outcomes And Measures: The primary end point was the incidence of somatic mutations of the RAS, BRAF, and EGFR genes and association of cetuximab efficacy with these mutations was investigated by using Fisher test. Secondary end points were the disease control rate (DCR) at week 6, the progression free-survival (PFS), overall survival (OS), and safety profile of cetuximab.

Results: Thirty-one samples of cSCC from 31 patients were analyzed. Only 2 RAS mutated samples (6.5%) were identified. The first harbored a NRAS point mutation (c.35G>A) in codon 12, resulting in a p.G12D substitution. The second sample presented a HRAS point mutation (c.38G>T) in codon 13, resulting in a p.G13V substitution. No mutation of KRAS, BRAF, and EGFR genes at the investigated loci was found. Two patients with NRAS and HRAS mutations showed a partial and complete response to cetuximab, respectively. The mean duration of follow-up was 19 months. At week 6, the disease control rate was 67.8%. The median OS was 13 months and the median PFS was 9 months. All patients could continue cetuximab treatment without dose reduction.

Conclusions And Relevance: Even in elderly patients with advanced cSCC, cetuximab was efficacious and well-tolerated. This suggests that cetuximab is certainly warranted in the treatment of advanced cSCC. However, it is also important to identify tumor specific mutations that may determine response to treatment and prognosis for the disease. We have identified here that the incidence of RAS, BRAF, and EGFR mutations is low in cSCC.
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April 2017

Peritoneal carcinomatosis of colorectal cancer: novel clinical and molecular outcomes.

Am J Surg 2017 Feb 5;213(2):377-387. Epub 2016 Aug 5.

Department of General Surgery and Digestive Cancerology, Nice University Hospital, 151 route de St. Antoine de Ginestière, Nice, 06200, France.

Background: The objective of this study was to identify the prognostic impact of parameters in peritoneal carcinomatosis from colorectal cancer.

Methods: We collected data from patients treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy for peritoneal carcinomatosis secondary to colorectal cancer.

Results: Ninety-one procedures were performed. In univariate analysis, an increased peritoneal cancer index was associated with decreased survival (P < .001). The presence of signet ring cells was associated to a decrease in survival from 45.8 to 12.1 months (P < .001). Microsatellite sequences instability status was the only molecular prognostic factor correlated with an increase in median disease-free survival: 12.4 vs 24.9 months (P = .01). The presence of a mucinous component was associated with a decreased of survival from 51.9 to 35.1 months (P = .02).

Conclusions: Clinical factors were affecting the survival of patients. The absence of signet ring cells and mucinous component and the presence of microsatellite sequences instability may be favorable prognostic factors.
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February 2017

Challenging a dogma: co-mutations exist in MAPK pathway genes in colorectal cancer.

Virchows Arch 2016 Oct 11;469(4):459-64. Epub 2016 Jul 11.

Molecular Pathology Unit, Institut Bergonié, 229 Cours de L'Argonne, 33076, Bordeaux, France.

Sequencing of genes encoding mitogen-activated protein kinase (MAPK) pathway proteins in colorectal cancer (CRC) has established as dogma that of the genes in a pathway only a single one is ever mutated. We searched for cases with a mutation in more than one MAPK pathway gene (co-mutations). Tumor tissue samples of all patients presenting with CRC, and referred between 01/01/2008 and 01/06/2015 to three French cancer centers for determination of mutation status of RAS/RAF+/-PIK3CA, were retrospectively screened for co-mutations using Sanger sequencing or next-generation sequencing. We found that of 1791 colorectal patients with mutations in the MAPK pathway, 20 had a co-mutation, 8 of KRAS/NRAS, and some even with a third mutation. More than half of the mutations were in codons 12 and 13. We also found 3 cases with a co-mutation of NRAS/BRAF and 9 with a co-mutation of KRAS/BRAF. In 2 patients with a co-mutation of KRAS/NRAS, the co-mutation existed in the primary as well as in a metastasis, which suggests that co-mutations occur early during carcinogenesis and are maintained when a tumor disseminates. We conclude that co-mutations exist in the MAPK genes but with low frequency and as yet with unknown outcome implications.
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October 2016