Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: Genetic Analysis of Birt Hogg-Dube Syndrome and Characterization of Predisposition to Kidney Cancer

Summary: This study will investigate the genetic cause of Birt Hogg-Dube (BHD) syndrome and the relationship of this disorder to kidney cancer. BHD is a rare inherited condition characterized by papules, or bumps benign tumors involving hair follicles on the head and neck. People with BHD are at increased risk of developing kidney cancer. Scientists have identified the chromosome (strand of genetic material in the cell nucleus) that contains the BHD gene and the region of the gene on the chromosome. This study will try to learn more about:
  -  The characteristics and type of kidney tumors associated with BHD
  -  The risk of kidney cancer in people with BHD
  -  Whether more than one gene causes BHD
  -  The genetic mutations (changes) responsible for BHD
  Patients with known or suspected Birt Hogg-Dube syndrome, and their family members, may be eligible for this study. Candidates will be screened with a family history and review of medical records, including pathology reports for tumors, and films of computed tomography (CT) and magnetic resonance imaging (MRI) scans.
  Participants may undergo various tests and procedures, including the following:
  -  Physical examination
  -  Review of personal and family history with a cancer doctor, cancer nurses, kidney surgeon, and genetic counselor
  -  Chest and other x-rays
  -  Ultrasound (imaging study using sound waves)
  -  MRI (imaging study using radiowaves and a magnetic field)
  -  CT scans of the chest and abdomen (imaging studies using radiation)
  -  Blood tests for blood chemistries and genetic testing
  -  Skin evaluation, including a skin biopsy (surgical removal of a small skin tissue sample for microscopic evaluation)
  -  Cheek swab or mouthwash to collect cells for genetic analysis
  -  Lung function studies
  -  Medical photography of skin lesions
  These tests will be done on an outpatient basis in either one day or over 3 to 4 days. When the studies are complete, participants will receive counseling about the findings and recommendations. Patients with kidney lesions may be asked to return periodically, such as every 3 to 36 months, based on their individual condition, to document the rate of progression of the lesions.

Detailed description: Background
  -  BHD is a rare, autosomal dominantly inherited disorder which confers susceptibility to develop multifocal, bilateral renal cancer, spontaneous pneumothorax and fibrofolliculomas.
  -  BHD is caused by mutations in the BHD gene located on Chromosome17p11.2.
  -  Defining the genetic and biochemical pathways leading to renal tumorigenesis in BHD may lead to the development of new molecularly targeted drugs.
  Objectives
  -  To define the types and characteristics (including patterns of growth) of renal cancer associated with BHD.
  -  To determine the risk of renal cancer, lung cysts and fibrofollicullomas in patients with BHD.
  -  To define the natural history of BHD related renal tumors.
  -  To determine if other genes contribute to BHD.
  -  Identify genotype / phenotype correlations.
  Eligibility
  -  Patients with histologically confirmed fibrofolliculomas.
  -  Patients with clinical evidence of multiple skin papules consistent with fibrofolliculomas, and a family history of spontaneous pneumothorax or kidney cancer.
  -  A relative of a patient with a confirmed diagnosis of BHD.
  -  Patients with a known germline BHD mutation.
  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 the BHD gene and to assess the relative activity of various germline and somatic mutations.
  -  We will determine if there is a relationship between mutation and disease phenotype.

Eligibility: -  INCLUSION CRITERIA:
  Patients with known or suspected Birt Hogg Dube Syndrome and their family members of any age will be recruited from the dermatology, urology, oncology, and genetics communities worldwide.
  Patients with at least one histologically confirmed fibrofolliculomas; or
  Patients with clinical evidence of multiple skin papules (without fibrofolliculoma biopsy confirmation) and a personal or family history of spontaneous pneumothorax / or kidney cancer; or
  Patients with spontaneous pneumothorax and skin papules or kidney cancer and a positive family history of spontaneous pneumothorax, skin papules or kidney cancer; or
  A relative of a patient with a confirmed diagnosis of BHD, or
  Renal tumor histology consistent with BHD, including, but not limited to those suggestive of chromophobe, oncocytic neoplasm oroncocytoma.
  EXCLUSION CRITERIA:
  Persons unable to give informed consent.

Relevance to patient case: not relevant