Christian Brambilla

Christian Brambilla
University Joseph Fourier - Grenoble 1 | UJF · Grenoble Institut de Recherche sur le Cancer

MD

About

422
Publications
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17,354
Citations

Publications

Publications (422)
Article
Full-text available
Circulating tumor DNA (ctDNA) is emerging as a key potential biomarker for post-diagnosis surveillance but it may also play a crucial role in the detection of pre-clinical cancer. Small-cell lung cancer (SCLC) is an excellent candidate for early detection given there are no successful therapeutic options for late-stage disease, and it displays almo...
Article
Plasma circulating cell-free (cf)DNA is of interest in oncology because it has been shown to contain tumour DNA and may thus be used as liquid biopsy. In nonsmall cell lung cancer (NSCLC), cfDNA quantification has been proposed for the monitoring and follow-up of patients. However, available studies are limited and need to be confirmed by studies w...
Article
Full-text available
Response Evaluation Criteria in Solid Tumors (RECIST) are widely used to assess the effect of chemotherapy in patients with cancer. We hypothesised that the change in unidimensional tumour size handled as a continuous variable was more reliable than RECIST in predicting overall survival (OS). The prospective Pharmacogenoscan study enrolled consecut...
Article
Full-text available
Purpose: The basaloid carcinoma (pure) and the (mixed) basaloid variant of lung squamous cell carcinoma (SCC) have a dismal prognosis but their underlying specific molecular characteristics remain obscure and no therapy has proven to be efficient. Experimental design: To assess their molecular specificity among other lung SCCs we analyzed DNA co...
Conference Paper
Lung neuroendocrine tumors (LNETs) comprise small-cell lung cancer (SCLC), large-cell neuroendocrine tumors (LCNEC), and pulmonary carcinoids (PCA), and account for 25% of all lung cancer cases. The low 5-year survival rate of the highly aggressive LNETs (SCLC and LCNEC) combined with the lack of an effective treatment, suggest that understanding h...
Article
Aims: Ectopic activation of tissue-specific genes accompanies malignant transformation in many cancers. Prolactin (PRL) aberrant activation in lung cancer was investigated here to highlight its value as a biomarker. Results: PRL is ectopically activated in a subset of very aggressive lung tumors, associated with a rapid fatal outcome, in our coh...
Article
Full-text available
Unlabelled: We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 le...
Article
We discovered a novel somatic gene fusion, CD74–NRG1 , by transcriptome sequenc-ing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocar-cinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74–NRG1 leads to ext...
Article
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We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment appro...
Article
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Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic c...
Article
Full-text available
PURPOSECharacterization of the genomic changes that drive an individual patient's disease is critical in management of many cancers. In patients with non-small-cell lung cancer (NSCLC), obtaining tumor samples of sufficient size for genomic profiling on recurrence is often challenging. We undertook this study to compare genomic alterations identifi...
Article
We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment appro...
Article
Objectives Platinum-based chemotherapy regimens are the standard treatment of non-small cell lung cancer (NSCLC). In this study, our objective was to identify tumor tissue protein biomarkers that might predict a benefit from these treatments. Materials and Methods The Pharmacogenoscan study prospectively included consecutive chemotherapy-naive NSC...
Article
Full-text available
Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis. We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 ± 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analyses of the various data sets to identify pathogenetically...
Article
Standard treatment of small-cell lung cancer (SCLC) is a combination of etoposide and platinum for patients with extensive disease, associated with radiotherapy for patients with limited disease (LD). Therapeutic strategies for relapse, although well characterized, are disappointing. Between 1997 and 2009, 300 patients were treated for SCLC at Gren...
Article
Full-text available
To study endobronchial cancers occurring in a population at high risk of bronchial cancer (history of surgically treated bronchial or ENT cancer in complete remission, and symptoms due to smoking) detected by annual volume CT scans and biannual fibroscopy. Two hundred and sixty-six patients were included in this single centre prospective study; 27...
Article
Objectif Étudier les cancers endobronchiques survenus dans une population à haut risque de cancer bronchique (antécédents de cancer bronchique ou ORL opérés en rémission complète, tabagiques symptomatiques) dépistés par TDM volumique annuelle et fibroscopie bi-annuelle. Patients et méthodes Deux cent soixante-six patients sont inclus dans cette ét...
Article
Full-text available
Background Environmental epidemiology and biomonitoring studies typically rely on biological samples to assay the concentration of non-persistent exposure biomarkers. Between-participant variations in sampling conditions of these biological samples constitute a potential source of exposure misclassification. Few studies attempted to correct biomark...
Data
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Statistical appendix.
Data
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Table S1. Limits of Detection of Urinary Phthalates Metabolites and Phenols and Detection Frequency Among FrenchPregnant Women from Eden and Pelagie Cohorts, 2002 – 2006. Table S2. Correlation coefficients between Phthalates Monoesters Metabolites and Phenols Crude Urinary Concentrations Among French Pregnant Women from Eden and Pelagie Cohorts, 20...
Article
Full-text available
Clinically, our ability to predict disease outcome for patients with early stage lung cancer is currently poor. To address this issue, tumour specimens were collected at surgery from non-small cell lung cancer (NSCLC) patients as part of the European Early Lung Cancer (EUELC) consortium. The patients were followed-up for three years post-surgery an...
Article
Full-text available
Antiangiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway have yielded more modest clinical benefit to patients with non-small-cell lung cancer (NSCLC) than initially expected. Clinical data suggest a distinct biologic role of the VEGF pathway in the different histologic subtypes of lung cancer. To clarify the influen...
Article
Full-text available
Nonsmall cell lung cancer samples from the European Early Lung Cancer biobank were analysed to assess the prognostic significance of mutations in the TP53, KRAS and EGFR genes. The series included 11 never-smokers, 86 former smokers, 152 current smokers and one patient without informed smoking status. There were 110 squamous cell carcinomas (SCCs),...
Article
Full-text available
We describe a case of extramedullary tracheal plasmacytoma that was incidentally discovered in a 73-year-old man on a PET scan performed for assessing the extent of colon cancer. CT scan showed the tumor; multiplanar reformation coupled with virtual bronchoscopy allowed proper treatment planning. The tracheal tumor was resected during rigid broncho...
Article
Full-text available
Data concerning the effects of prenatal exposures to phthalates and phenols on fetal growth are limited in humans. Previous findings suggest possible effects of some phenols on male birth weight. Our aim was to assess the relationships between prenatal exposures to phthalates and phenols and fetal growth among male newborns. We conducted a case-con...
Article
Lung cancer screening has entered a new era since few months. 30 years ago, four main trials showed the lack of benefit of screening in terms of lung cancer mortality using chest radiography with or without sputum cytology. Spiral CT was introduced 15 years ago as a technique for screening lung cancer. Many observational studies showed that CT demo...
Article
Full-text available
The incidence of adenocarcinoma is increasing, particularly among females. We sought to assess the role of tobacco consumption in clinical presentation according to sex. In this retrospective study, 848 patients diagnosed between 1997 and 2006 at Grenoble University Hospital (Grenoble, France) were stratified into four groups according to smoking h...
Article
In a European multicenter prospective study patients with lung cancer were interviewed for smoking history and biological samples centrally collected. The aim of this study was to compare KRAS mutation analysis with smoking status at the time of diagnosis. A nested case-study was performed on 233 non-small cell lung carcinomas. Cases were selected...
Article
Full-text available
We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensi...
Article
Sodium butyrate (NaBu) is a histone deacetylase inhibitor that exhibits numerous antiproliferative activities in various cancer cell lines, notably through the accumulation of the well-known cyclin-dependent kinase inhibitor p21(WAF1) . SRSF2 belongs to the family of SR proteins that are crucial regulators of constitutive and alternative pre-mRNA s...
Article
Vascular endothelial growth factor A (VEGFA) mediates its effects through VEGFR1 and VEGFR2, regulating angiogenesis in healthy and tumor tissues. Hence, an anti-VEGFA therapy has been approved, in combination with platinum-based chemotherapy, as first line treatment in unresectable advanced non-small cell lung cancer (NSCLC). This antiangiogenic t...
Article
Full-text available
Unlabelled: While genomically targeted therapies have improved outcomes for patients with lung adenocarcinoma, little is known about the genomic alterations which drive squamous cell lung cancer. Sanger sequencing of the tyrosine kinome identified mutations in the DDR2 kinase gene in 3.8% of squamous cell lung cancers and cell lines. Squamous lung...
Article
Full-text available
SRSF2 is a serine/arginine-rich protein belonging to the family of SR proteins that are crucial regulators of constitutive and alternative pre-mRNA splicing. Although it is well known that phosphorylation inside RS domain controls activity of SR proteins, other post-translational modifications regulating SRSF2 functions have not been described to d...
Article
Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respira...
Article
Full-text available
Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically e...
Article
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ING2 (inhibitor of growth 2) is a candidate tumor-suppressor gene involved in cell cycle control, apoptosis and senescence. Although the functions of ING2 within the chromatin remodeling complex Sin3A/histone deacetylase (HDAC) and in the p53 pathway have been described, how ING2 itself is regulated remains unknown. In this study we report for the...
Article
ING2 (Inhibitor of Growth 2) is a candidate tumor suppressive protein frequently lost in human tumors. Recently, we have reported that ING2 downregulation impairs DNA replication forks progression and leads to genome instability. To better understand the tumor suppressive functions of ING2 and its role in the cell cycle, we downregulated its expres...
Article
Full-text available
The transcription factor E2F1 has a crucial role in the control of cell growth and has been shown to regulate neoangiogenesis in a p53-dependent manner through inhibition of activity of the VEGF-A (vascular endothelial growth factor) promoter. Besides being regulated by transcription, VEGF-A is also highly regulated by pre-mRNA alternative splicing...
Article
Full-text available
Cancer cells frequently express genes normally active in male germ cells. ATAD2 is one of them encoding a conserved factor harbouring an AAA type ATPase domain and a bromodomain. We show here that ATAD2 is highly expressed in testis as well as in many cancers of different origins and that its high expression is a strong predictor of rapid mortality...
Article
Full-text available
Lung cancer is the most important cause of cancer-related mortality. Resectability and eligibility for treatment with adjuvant chemotherapy is determined by staging according to the TNM classification. Other determinants of tumour behaviour that predict disease outcome, such as molecular markers, may improve decision-making. Activation of the gene...
Data
French validation of clustering results. (0.29 MB TIF)
Data
Japanese validation of clustering results. (2.45 MB TIF)
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French validation of survival differences of clusters. (0.10 MB TIF)
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French validation of solid subtype survival differences. (0.08 MB TIF)
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References for gene lists (0.05 MB DOC)
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Gene lists for all pathways with probe sets. (1.09 MB XLS)
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Japanese pathway-pathology interactions. (0.03 MB DOC)
Data
United States multivariate Pathology Survival using Percent Component (0.03 MB DOC)
Data
French gene enrichment p-values. (0.05 MB DOC)
Data
Additional United States gene enrichment data. (0.06 MB DOC)
Data
Additional United States pathology-pathway data - acinar (+/−). (0.04 MB DOC)