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The goal of this study is to comprehensively map intra and inter tumor heterogeneity of ccRCC in VHL patients through the use of imaging, molecular biology and genomics techniques.
It was hypothesized that the high intra- inter-tumor heterogeneity of sporadic ccRCC also defines VHL-ccRCCs, including different lesions within individual patients, and it was assumed that decoding VHL-ccRCC heterogeneity by coupling imaging, histology and molecular profiling of multiregional biopsies would help improve diagnostic tests and therapeutic choices for VHL patients.
In order to comprehensively map intra and inter tumor heterogeneity of ccRCC in VHL patients, the aims of the study are:
This study will develop standardized models for diagnosis and molecular characterization of ccRCC in VHL disease using a combination of imaging, intrasurgical biopsying and multi-omics analysis. It will benefit of a clinical and research program devoted to VHL disease established at OSR in 2021 that centralizes Italian VHL patients. Since the current study relies on tumor biopsy techniques that are already established in clinical practice, the translational findings will be directly available and immediately affecting patients' care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VHL patients | Patients with hereditary Von Hippel-Lindau (VHL) with genetic diagnosis of VHL disease who have at least three tumors larger than 3cm that have to be surgically removed. The procedure involves standard surgery with the additional collection of 15ml of blood. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood collection | Other | 15ml of blood are harvested before surgery |
|
| Measure | Description | Time Frame |
|---|---|---|
| Integrating Imaging and multiregion biopsy sampling in VHL related ccRCC | Pre-surgery imaging will be integrated using conventional multiparametric MRI with tumor histology of geographical predeterminated multi-region biopsies in each ccRCC of VHL patients. | From month 3 to month 20 |
| Determine immune and stromal heterogeneity in VHL-ccRCC | Multiplex immunohistochemistry, bulk and single cell RNA sequencing and somatic mutations analysis with pan-tumor histological assessment will be combined. | DNAseq and bulk RNAseq will be carried out from month 7 until month 20. Multiplex immunohistochemistry (IHC) in multiregional biopsies and standard IHC on the whole tumors will be performed the last 12 months of the study. |
| Generation and characterization of VHL-ccRCC patient-derived organoids | A protocol to generate VHL-ccRCC-derived tumor organoids (patient-derived organoids, PDO) will be optimized to test anti tumor agents like HIF2alpha inhibitor in organoid cultures representative of intra- and inter-tumor heterogeneity. | From month 3 until the end of the project. |
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Inclusion Criteria:
Exclusion Criteria:
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VHL patients with at least 3 kidney tumors larger that 3cm to be surgically removed
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| IRCCS Ospedale San Raffaele | Milan | MI | 20132 | Italy |
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| ID | Term |
|---|---|
| D002292 | Carcinoma, Renal Cell |
| D006623 | von Hippel-Lindau Disease |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Pan-tumor histological assessment through molecular and histopathological evaluation
| D009369 | Neoplasms |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D020752 | Neurocutaneous Syndromes |
| D009422 | Nervous System Diseases |
| D000798 | Angiomatosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000072661 | Ciliopathies |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |