Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Melanoma

Summary: This study will investigate how genetic and environmental factors contribute to the development of melanoma, a type of skin cancer, and related conditions.
  Individuals of any age with a personal or family history of melanoma may be eligible for this study. Participants will:
  -  Fill out one or two questionnaires about their personal and family medical history.
  -  Provide written consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with melanomas, tumors, cancer, or other related illnesses for whom they are the next-of-kin or legally authorized representative.
  -  Donate a blood or cheek cell sample to be used for genetic studies. (The blood sample is collected through a needle in an arm vein. The cheek cell sample is obtained either by gently brushing the inside of the mouth with a soft brush or by swishing a tablespoon of mouthwash and then spitting it into a container.)
  -  Undergo a skin biopsy (removal of a small piece of skin tissue) for genetic study. For this procedure, the area of skin to be removed is numbed with a local anesthetic and a 1/4-inch piece of skin is excised with a cookie cutter-like instrument. The wound is then covered with a band-aid.
  Participants may be asked to travel to the NIH Clinical Center for evaluation, including a medical history, physical examination, and some of the following procedures:
  -  Full body skin examination to evaluate the type and number of moles and document any evidence of sun damage to the skin. The examination involves all the skin from the scalp to the bottoms of the feet. After the examination, a medical photographer will photograph the skin, with close-ups of skin lesions marked by the examiner. If there are parts of the skin the participant does not want examined or photographed, he or she can tell the examiner.
  -  Blood draw of about 120 milliliters (4 ounces) or less
  -  Skin biopsy
  -  Cheek cell sample
  -  X-rays, ultrasound and magnetic resonance imaging (MRI) studies to detect tumors or changes in tumors or other types of changes in specific tissues. MRI is a diagnostic test that uses strong magnetic fields and radiowaves to examine body tissues. The subject lies on a table that is moved into a large tunnel-like machine (the scanner) for about 45 minutes to 1 hour.
  When the tests are finished, a doctor will discuss the results with the participant and the need, if any, for clinical follow-up.

Detailed description: Background:
  -  Persons may be prone to develop melanoma for a variety of reasons including: family history; environmental exposures; other malignant or premalignant conditions which may or may not be heritable; immune deficiency; or, preneoplastic conditions such as dysplastic nevi.
  -  Investigations of individuals and families at high risk of melanoma have led to etiologic clues that are important in the general population.
  -  Identification of melanoma susceptibility genes, the estimation of their effects, and gene-covariate and gene-gene interactions could improve prevention, screening and treatment of this cancer.
  Objectives:
  -  To evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing to melanoma.
  -  To evaluate potential precursor states of disease in families at risk.
  -  To quantify risks of melanoma, pancreatic cancer, and other cancers in family members.
  -  To map, clone, and determine function of tumor susceptibility genes in melanoma-prone families, including modifier genes such as pigmentation or dysplastic nevi genes.
  -  To identify genetic determinants and gene-environmental interactions conferring melanoma (and other cancer) risk in individuals and families.
  -  To evaluate gene-gene and gene-environment interactions in melanoma (and other cancer) formation.
  -  To educate and counsel study participants about their melanoma risk and methods for primary and secondary prevention of melanoma.
  -  To develop educational materials for medical professionals and high-risk family members.
  Eligibility:
  Persons of any age will be considered if,
  -  There is a family or personal medical history of melanoma of an unusual type, pattern, or number; or,
  -  There are known or suspected factor(s) predisposing to melanoma, either genetic or congenital factors, or unusual demographic features.
  -  For familial melanoma, three or more living affected cases with invasive melanoma among family members are required.
  Design:
  -  This is a prospective study. Families are studied long-term using a cohort approach.
  -  Two melanoma susceptibility genes have been identified, but it is likely others are yet to be found. We are also exploring potential modifier genes in participating families.
  -  The affection status of each participant, information on their skin examination, sun exposure history, medical photographs (both overview and close-up) and blood draw for localizing genetic loci, identifying genes and evaluating phenotype/genotype correlations, constitute the workup for newly recruited families.
  -  Study volunteers are reevaluated every few years to document changes in their skin exam over time. This is essential for establishing the natural history of dysplastic nevi and melanoma.

Eligibility: -  INCLUSION CRITERIA:
  -  On referral, persons of any age will be considered for inclusion in the study because of either:
  -  A family or personal medical history of melanoma of an unusual type, pattern, or number; or
  -  Known or suspected factor(s) predisposing to melanoma, either genetic or congenital factors (bathing trunk nevi, dysplastic nevi), or unusual demographic features (e.g. very young age of onset, multiple melanomas, previous history of heritable retinoblastoma, Hodgkin's disease, lymphoma, or organ transplant).
  EXCLUSION CRITERIA:
  -  Referred individuals and families for whom reported diagnoses cannot be verified;
  -  Inability to provide informed consent.

Relevance to patient case: not relevant