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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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Endometrial cancer (EC) is one of the most common gynecological neoplasms, being the second in incidence and third in mortality in Mexico. Recent studies show that EC molecular classification (Cancer Genome Atlas Research Network, 2013) serves to establish a more accurate prognosis in these patients and regulate therapeutic behavior in a personalized manner. However, there are no studies on EC molecular classification in Mexican women or its impact on prognosis and the possible modification of targeted treatment. The investigators will determine the molecular classification in EC by next-generation sequencing (NGS) to detect TP53 and POLE somatic mutations, and immunohistochemical detection of microsatellite instability (MSH2, MLH1, PMS1, PMS2, MSH6, and MSH3) in a cohort of patients with endometrioid-type EC, endometrioid subtype, attended at the Instituto Nacional de Cancerología - Mexico (INCan) and determine its impact on clinical prognosis.
The investigators will carry out a pilot study on patients with endometrioid type EC treated between 2015-2019. Samples of patients over 18 years of age admitted to the cohort with a diagnosis of endometrioid-type EC are already collected and will be evaluated for exome sequencing (N=32) and the detection of POLE mutations. DNA will be extracted using the "DNA/RNA AllPrep" kit (QIAGEN). Verification of adequate DNA extraction will be performed by quantifying using TapeStation (Agilent). Exome sequencing (N = 32 tumor samples and 32 somatic samples [leukocytes] from the same patient) will be carried out using Illumina's Nextera Rapid Capture Exome at Azenta Life Science (NJ, USA) following preset protocols and with a depth of 100X. The alignment and detection of variants will be done with the GATX-Mutect Suite (Broad Institute, USA) and the annotation of variant filtering with ANNOVAR. The identification of hotspots will be made according to Chen study. The immunohistochemistry (IHC) for microsatellite instability and overexpressed mutant TP53 (N = 94) will be done using established IHC protocols and will include MSH2, MLH1, PMS1, PMS2, MSH6, MSH3, and TP53.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with EC endometroid | Patients with EC endometroid subtype and peripheral blood, treated during 2015-2019 at the INCan. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Descriptive and analytical | Genetic | Patients with EC endometroid |
|
| Measure | Description | Time Frame |
|---|---|---|
| sequence the exome | Molecular classification of endometroid-type endometrial cancer in Mexican participants based on POLE and TP53 mutations as well as makers of microsatellite instability (MSH2, MLH1, PMS1, PMS2, MSH6, and MSH3). | 2024-2025 |
| Determine POLE mutations | Determine POLE mutations by massive next-generation sequencing of a discovery cohort in patients with endometroid-type EC. | 2024-2025 |
| Determine microsatellite instability | To perform validation of POLE mutation by real-time PCR in a validation cohort of patients with endometroid-type EC. | 2025-2026 |
| Validation | To perform validation of POLE mutation by real-time PCR in a validation cohort of patients with endometroid-type EC. | 2025-2026 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival | To describe the overall survival of molecular types of endometroid-type EC in INCan patients. | 2025-2026 |
| Disease-free surviva | To describe the disease-free survival of the molecular types of endometroid-type EC in INCan patients. |
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Criteria: Inclusion Criteria:
Exclusion Criteria:
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We will evaluate samples from females with endometrioid type EC t
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The investigators will evaluate samples from patients with endometrioid type EC treated between 2015-2019. Samples of patients over 18 years of age admitted to the cohort with a diagnosis of endometrioid-type EC are already collected and will be evaluated for exome sequencing (N=32) for the detection of POLE mutations.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| David F Cantu-de-León, PhD | Contact | +52-55-5628-0400 | 21016 | dfcantu@gmail.com |
| Diddier Prada, PhD | Contact | +52-55-41-42-18-02 | pradadiddier@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| David F Cantu-de-León, PhD | The Principal Investigator | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto Nacional de Cancerología | Recruiting | Mexico City | Mexico City | 14080 | Mexico |
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Any time by direct request to the principal investigator
Only for research purposes.
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| ID | Term |
|---|---|
| D016889 | Endometrial Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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Paraffin embeamed samples
| 2025-2026 |
| D009369 |
| Neoplasms |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |