Neoplasms

All Conditions

Behaviors and Mental Disorders

Rare Diseases

Oligodendroglioma

Aggression

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

the more aggressive subgroup of oligodendroglioma samples of 30 patients

subgroup 2 of oligodendroglioma samples of 30 patients

subgroup 3 of oligodendroglioma samples of 30 patients

patients with IDH-mutant astrocytomas, samples of 15 patients

patients with IDH-wildtype glioblastomas, samples of 15 patients

: Proteomic analysis in the 3 subgroups of oligodendrogliomas (O1, O2 and O3) and in the comparator groups of IDH-mutant astrocytomas, IDH-wildtype glioblastomas and normal brain samples

Proteomic analysis

François DUCRAY, MD

François Ducray, MD

Oligodendrogliomas represent a distinct subgroup of adult gliomas characterized by specific molecular alterations (1p/19q codeletion, mutations of IDH, TERT promoter, CIC, FUBP1). These tumors account for 5 to 10% of adult gliomas and are of special relevance in the neuro-oncology field because of their frequent chemosensitivity (Louis et al. 2016). The genetics of oligodendrogliomas is relatively well characterized but the mechanisms of oncogenesis for these tumors are poorly understood.

Although oligodendrogliomas prognosis is usually better than that of other adult glioma subtypes, it remains heterogeneous and there is no effective treatment at recurrence after radiotherapy and chemotherapy. Our recent work conducted within the INCa-funded national POLA network has related this clinical heterogeneity to inter-tumoral heterogeneity. Based on a transcriptomic analysis of a large series of oligodendroglial gliomas we identified 3 subgroups, the most aggressive group being characterized by aggressive clinical and molecular pattern. Recent studies, however, have shown a relatively low level of concordance between mRNA and protein expression, emphasizing the need to use proteomic-based approaches to better understand tumor biology. Taking advantage of the POLA cohort, we propose to expand our previous analysis by integrating a proteomic analysis of oligodendrogliomas.

The aim of this project is to identify drivers of oligodendroglioma subgroups, among which potential druggable targets (i.e receptors, metabolism effectors). For this purpose, the proteomic profiles of 90 oligodendrogliomas will be generated and integrated with transcriptomic, genomic and methylation profiles in order to identify signaling pathways specifically associated with each subtype, especially with the most aggressive one. Associations will be explored between candidate signaling pathways expression and clinical outcomes (survival, progression-free survival, objective response). The relevance of the 2 most promising candidate signaling pathways will be assessed in vitro and in vivo using genetically relevant mouse and xenograft models.

Our project will identify targetable oncogenic pathways associated with poor prognosis that could lead to new therapeutic strategies.

Proteomic Characterization of Aggressive Oligodendrogliomas

Concordance of the classification of oligodendrogliomas based on their proteomic profiles with our previously identified oligodendrogliomas subgroups.

Hospices Civils de Lyon

Carcinoma

Adenocarcinoma

Anne RULLIER, MD

Paul PEREZ, MD

Treatment for locally-advanced rectal adenocarcinoma includes preoperative radiochemotherapy before surgery with total mesorectal excision in order to reduce tumor infiltration, facilitate oncologic surgery and improve survival. About fifty percent of these patients are good responders i.e. their tumor infiltration reduces in the rectal wall and regional lymph nodes in order to be graded ypT0 to T2 N0 after pathologic assessment (so called downstaging). At the opposite, bad responders (ypT3-4 and/or N+) are not sensitive to standard preoperative radiochemotherapy, and their survival is poor than good responders. Until now, response to preoperative radiochemotherapy cannot be anticipated before pathological assessment of surgical specimen. Proteomic analysis of sera from good and bad responders to preoperative radiochemotherapy could allow identification of early biomarkers of tumor response, and subsequently adaptation of treatment to increase preoperative treatment efficiency and survival in most patients.

Good or bad responders to preoperative radiochemotherapy for locally-advanced rectal adenocarcinoma cannot be anticipated before pathological assessment of rectal specimen. The purpose of this prospective monocentric study is to look for early seric biomarkers predictive of tumor response (good and bad responders) in patients treated by preoperative radiochemotherapy (45 Gy) for rectal adenocarcinoma using a proteomic approach. All patients with locally-advanced rectal adenocarcinoma will be enrolled. Sequential samples of sera will be collected before, during preoperative treatment and before surgery, and analysed using a MALDI-TOF-TOF method. Proteomic analysis will be correlated to pathological response in order to identify potential early biomarkers of tumor response.

Proteomic Approach Using Matrix-assisted Laser Desorption/Ionization Tandem Time-of-flight (MALDI-TOF/TOF) of Tumor Response in Rectal Carcinoma After Radiochemotherapy

University Hospital, Bordeaux

Post-mortem oncological patients (within 2-6 hrs from death, maximum time for tissue preservation).

Proteomic analysis of tissues collected from all sites of disease, guided by either imaging performed prior to the patient's death or post-mortem findings. Peripheral blood mononuclear cells (PBMC) will be collected with the purpose of identifying somatic changes occurring specifically in the tumor cells and not in normal DNA of the same patient.

Salvatore Siena, MD

DONUM is an observational prospective independent protocol for patients with advanced lung cancer, colorectal cancer or cancer of unknown primary, willing to donate their tumor tissue samples post mortem for biomedical research purposes. All patients who fulfill the inclusion criteria will be eligible for the study after giving their Informed consent. Informed Consent will be obtained in two steps. During the pre-information step patients will be acquainted with the existence of a post-mortem cancer tissue donation research program governed by the DONUM protocol. If the patients manifest interest to participate into the program (in writing) during the pre-information step, they will proceed to step 2 and undergo the final informed consent process.

Despite the recent technological advancement in genomic and proteomic, the molecular understanding of clonal evolution in solid tumor patients is hampered by intra tumor heterogeneity (ITH), while remaining essential to the effective treatment of patients. Recent evidence suggests that branched evolutionary tumor growth may contribute to ITH both within a primary tumor and between primary and metastatic tumors. To study the full extent and consequences of ITH, and grasp clonal evolution, the investigators need to have access not only to circulating biomarkers (circulating tumor DNA) but also, simultaneously and separately, to the primary tumor and all its derived metastases. However multiple biopsies in live patients are neither medically feasible, nor ethical acceptable. A lesser known tissue collection method is through rapid tissue donation (RTD), which is the procurement of 'fresh' tissue within 2 hrs following the death of a patient. RTD-based research provides an effective way to investigate advance tumors biology in a manner not possible by any other means. With an RTD approach, the full extent and consequences of tumor heterogeneity can be evaluated by deep sequencing and global analysis of genetic alterations at the protein level of simultaneous core biopsies from several areas of the primary tumor and metastases and correlation with clinical outcome. To investigators' knowledge, no such studies have been done in Italy and are currently being pursued only in selected USA and UK cancer centers.

Primary and metastatic tissues and peripheal blood samples

Donation of Post Mortem Tumor Tissues

Donation of Post Mortem Tumor Tissues to Unravel Cancer Heterogeneity

Procure primary and metastatic tissue of selected solid tumor patients shortly after death in order to investigate ITH (intratumor heterogeneity), using integrated genomic and proteomic analysis

Study ITH as a results of anticancer drugs exposure in order to forecast its potential impact on subsequent lines of therapy

Study how the genomic landscape provided by the determination of the circulating free tumor DNA (ctDNA) compare to the genomic landscape from all tumor tissues, considered as gold standard

University of Turin, Italy

Fondazione del Piemonte per l'Oncologia

Niguarda Hospital

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Small Cell Lung Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Small Cell

Lung Neoplasms

Neuroendocrine Tumors

Thymoma

Thymus Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lymphatic Diseases

Small Cell Lung Cancer

Neuroendocrine Tumor

Thymic Epithelial Tumor

Patients with histologically or cytologically confirmed NSCLC, SCLC, ESCC, PNET, and TET

Shannon G Swift, R.N.

Arun Rajan, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Background:

- Lung cancer is the leading cause of cancer-related death worldwide. It causes more than one million deaths every year. Researchers want to gather tissue samples from people with lung and thymic cancers to understand the disease better. This may lead to new ways to diagnose and treat it.

Objective:

- To collect tissue samples for use in the study of lung cancers.

Eligibility:

- Adults over age 18 with non-small cell lung cancer, small cell lung cancer, extra pulmonary small cell cancer, pulmonary neuroendocrine tumors, and thymic epithelial tumors.

Design:

* Participants will be screened with a medical history, physical exam, and blood tests. They will be asked about how they perform their daily tasks.
* Participants may be asked to give urine and blood samples. They may give a saliva sample if they cannot give blood. They will also give a sample of their tumor from a biopsy they had. They may also be given the option to undergo a biopsy.
* Participants may have MRI, CT, and/or PET scans of the body. They will lie in a machine that takes pictures of the body.
* After visits to the Clinical Center end, researchers will contact participants by phone every year to check on their health.

Background:

* Lung cancer is the leading cause of cancer-related death worldwide, accounting for more than one million deaths every year.
* Several genetic and epigenetic alterations are involved in initiation and progression of NSCLC. Some of these alterations are seen in normal and preneoplastic cells as well, suggesting a sequential development from normal epithelial cells to cancer, through a multistep process, usually coincident with cigarette smoking.
* This natural history protocol is an extension of our Molecular Profiling protocol to enable tissue collection for more in-depth proteomic and genomic analyses to understand tumor biology and treatment response.
* A cohort of patients enrolled in this natural history study is likely to enroll in the IRB approved protocol for end-of-life in-patient hospice and rapid autopsy following death (13-C0131). Longitudinally collected tumor tissue from these patients, including from several metastatic sites at autopsy will be a unique resource to understand tumor evolution.
* There will be opportunity to embark upon a wide array of studies in the future with the longitudinally collected tissue samples tagged with clinical information from patients.

Objectives:

- To allow sample acquisition for use in the study of non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC), extrapulmonary small cell cancer (ESCC), pulmonary neuroendocrine tumors (PNET), and thymic epithelial tumors (TETs).

Eligibility:

* Patients with histologically or cytologically confirmed NSCLC, SCLC, ESCC, PNET, and TET.
* Patients consulted in the Clinical Center without a definitive diagnosis, but clinically considered likely to have a thoracic malignancy of the above histologies, pending further tissue acquisition and/or pathology review.
* Age greater than or equal to 18 years.

Design:

* This is a bio-specimen collection and natural history protocol in which samples will be collected from patients with NSCLC, SCLC, ESCC, PNET, and TET.
* Eligible patients undergoing screening for or participating in NIH protocols or eligible patients treated elsewhere and referred from other oncologists will be referred for participation in this study.
* Upon providing informed consent, patients will undergo sample acquisition procedures, which may include a tumor biopsy, bone marrow biopsy or the collection of blood, urine or other body fluids.
* An accrual ceiling of 2000 subjects is planned over an accrual period of 10 years.

Tissue Procurement and Natural History Study of People With Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Extrapulmonary Small Cell Cancer, Pulmonary Neuroendocrine Tumors, and Thymic Epithelial Tumors

Tissue Procurement and Natural History Study of Patients With Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Extrapulmonary Small Cell Cancer, Pulmonary Neuroendocrine Tumors, and Thymic Epithelial Tumors

.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

blood, tumor, body fluids, and normal tissue samples

clinical data, including overall survival

Specific studies include, but not limited to genomic analyses using NGS technologies (exome, transcriptome and/or whole genome sequencing), DNA methylation analyses, DNA copy number analyses, proteomic studies including mass spectrometry, capillary Westerns, reverse phase protein microarrays (RPPA), luminex assays, ELISA and IHC, and metabolomics studies using mass spectrometry.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Proteomic Characterization of Aggressive Oligodendrogliomas	NCT04843085	Oligodendroglio...	Proteomic analy...	-	Hospices Civils de Lyon
Proteomic Approach Using Matrix-assisted Laser Desorption/Ionization Tandem Time-of-flight (MALDI-TOF/TOF) of Tumor Response in Rectal Carcinoma After Radiochemotherapy	NCT00855946	Rectal Adenocar...		18 Years - 80 Years	University Hospital, Bordeaux
Donation of Post Mortem Tumor Tissues	NCT03385980	NSCLC Stage IV CRC CUP	Proteomic analy...	-	Niguarda Hospital
Proteomic Approach Using Matrix-assisted Laser Desorption/Ionization Tandem Time-of-flight (MALDI-TOF/TOF) of Tumor Response in Rectal Carcinoma After Radiochemotherapy	NCT00855946	Rectal Adenocar...		18 Years - 80 Years	University Hospital, Bordeaux
Tissue Procurement and Natural History Study of People With Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Extrapulmonary Small Cell Cancer, Pulmonary Neuroendocrine Tumors, and Thymic Epithelial Tumors	NCT02146170	Non-Small Cell ... Small Cell Lung... Extrapulmonary ... Pulmonary Neuro... Thymic Epitheli...		18 Years -	National Institutes of Health Clinical Center (CC)
Proteomic Approach Using Matrix-assisted Laser Desorption/Ionization Tandem Time-of-flight (MALDI-TOF/TOF) of Tumor Response in Rectal Carcinoma After Radiochemotherapy	NCT00855946	Rectal Adenocar...		18 Years - 80 Years	University Hospital, Bordeaux
Tissue Procurement and Natural History Study of People With Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Extrapulmonary Small Cell Cancer, Pulmonary Neuroendocrine Tumors, and Thymic Epithelial Tumors	NCT02146170	Non-Small Cell ... Small Cell Lung... Extrapulmonary ... Pulmonary Neuro... Thymic Epitheli...		18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for proteomic analysis