ALK Gene Mutation, BAP1 Tumor Predisposition Syndrome, Birt-Hogg-Dube Syndrome, Cutaneous Leiomyoma, Cutaneous Leiomyomata With Uterine Leiomyomata, Familial Renal Cancer, FH Gene Mutation, FLCN Gene Mutation, HLRCC, Kidney Cancer, MET Gene Mutation, Renal Cell Carcinoma, Renal Tumor Histology, VHL Syndrome
Conditions
Brief summary
This study will investigate the frequency, clinical phenotype, management and molecular genetic defects of heritable kidney cancer syndromes. Families with kidney cancer with known or suspected genetic basis will be enrolled. Affected individuals or individuals suspected of having a germline kidney cancer will undergo periodic clinical assessment and genetic analyses for the purpose of: 1) definition and characterization of phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype correlation. Genetic linkage studies may be performed in situations in which the genetic basis of the disorder has not been elucidated. This research will have a significant impact on the overall management of heritable kidney cancer syndromes patients and family members who are at risk for heritable kidney cancer syndromes. The study will ultimately facilitate the development of novel screening, prevention and treatment strategies for these individuals with the syndrome. In addition this study could have impact on the management of patients with personal and/or family history of heritable kidney cancer syndromes.
Detailed description
Background: • The genetic etiology of heritable kidney cancer syndromes remains to be determined. Objectives: * Define the risk of developing renal cance in heritable kidney cancer syndromes * Define the types and characteristics (including patterns of growth) of heritable kidney cancer syndromes. * Determine genotype/phenotype correlations. * To characterize the natural and clinical histories of heritable kidney cancer syndromes. * To determine the genetic etiology of heritable kidney cancer syndromes. Design: * These rare families will be recruited to genetically confirm diagnosis, determine size and location of renal tumors, size at presentation, growth rate and metastatic potential of renal tumors. * Genetic testing will be offered to gain appreciation of the effect of mutations on the relative activity of various germline and somatic mutations. * To determine if there is a relationship between mutation and disease manifestations and phenotype.
Interventions
GENETICGene test
Next generation sequencing of blood, urine and/or benign and malignant tissue of patients and family members with known or suspected heritable kidney cancer syndromes, including VHL and HLRCC Disease.
Sponsors
Ruijin Hospital
Shanghai Zhongshan Hospital
Huashan Hospital
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Zhejiang Provincial People's Hospital
Tongji Hospital
Second Affiliated Hospital, School of Medicine, Zhejiang University
Shanghai 10th People's Hospital
First Affiliated Hospital, Sun Yat-Sen University
Peking University First Hospital
RenJi Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participants must be greater than or equal to 2 years of age. All patients and guardians (for children younger than 18 years of age) must sign an informed consent document indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed. Patients under the age of 18 but who are age 13 or older will be asked to sign an assent document prior to participation. * Individuals and biologic family members with a suspected or an established diagnosis of a heritable kidney cancer syndrome in which the disease gene is known, including von Hippel-Lindau (VHL) and hereditary papillary renal carcinoma (HPRC). * Individuals and biologic family members with a suspected or an established diagnosis of a heritable kidney cancer syndrome in which the disease gene is not yet known, specifically hereditary forms of Type II papillary renal cancer, clear cell renal carcinoma, renal oncocytoma, chromophobe renal carcinoma or Birt Hogg Dube. * Individuals and biologic family members who have heritable kidney cancer syndromes of suspected, but not proven genetic etiology, including families with more than one individual affected by the same or related cancers. * Subject Enrollment Categories (to include both affected and unaffected biologic relatives).
Exclusion criteria
* Pregnant women are excluded from enrollment onto this study because there is no direct benefit for participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical phenotypes of patients of heritable kidney cancer syndromes | 5 years | Chart review of disease outcome |
| Genotypes of patients of heritable kidney cancer syndromes | 5 years | Genotyping for genetic variants that could modify the risk of cancer in subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical phenotypes of family members of the patients | 5 years | Questionnaire and chart review of the clinical phenotype |
| Prevalence of germline variants in the unselected general population of renal cancer patients | 5 years | Frequency of germline pathogenic/likely pathogenic variants in renal cancer |
Countries
China
Contacts
Primary ContactYunze Xu, Ph.D.
Outcome results
None listed