Comprehensive MELARIS^® Test Result Case Examples
NO MUTATION DETECTED OR
GENETIC VARIANT OF UNCERTAIN SIGNIFICANCE

When the results of Comprehensive MELARIS^® indicate no mutation detected or genetic variant of uncertain significance, the patient's risk of cancer and recommendations for medical management must be based on the personal and family history of cancer. This section will provide you with information on how to approach negative test results, using case examples to illustrate important points.

The pattern of cancer in a family generally can be divided into three categories:

1. Hereditary – Hereditary cancer families are those in which a causative mutation in a specific gene has been identified through genetic testing, or those families with clinical histories that are strongly suggestive of a highly-penetrant gene mutation (multiple primary cancers, early age of onset, multiple generations affected). Hereditary cancer is the least common pattern of cancer.

2. Familial – Familial cancer families are those in which a few relatives have had the same or a related type of cancer, but the ages of diagnosis and pattern of affected relatives is not highly suggestive of a hereditary risk. Familial cancer clusters are most likely due to the combined effects of environmental factors, lifestyle habits, and many genes interacting together. A specific causative gene mutation cannot be identified in familial cancer.

3. Sporadic – Sporadic cancer families are those in which one or more relatives have developed common forms of cancer at typical ages, and there is no apparent pattern to the diagnoses. Sporadic cancer is the most common pattern of cancer.

When no definitive mutation is detected through Comprehensive MELARIS^®, the level of suspicion for continued hereditary cancer risk depends on the strength of the patient's personal and family history of cancer. Most published literature on cancer risk and recommendations for screening/prevention focus on the high risk and average risk groups. High risk cases include individuals who have tested positive for a gene mutation or who have a family history that is highly suggestive of hereditary risk; average risk cases include those individuals who do not have any significant risk factors for cancer. The screening and preventative recommendations for individuals with a moderately increased risk of cancer are less clear and are often based on expert opinion.

The cases below describe one approach to interpreting a Comprehensive MELARIS^® no mutation detected or genetic variant of uncertain significance result in various family history settings. These cases are not meant to be all inclusive. If you would like to discuss a specific patient history, or if you have additional questions, please contact the Myriad's Medical Services Department at 1-800-469-7423 or the Regional Medical Specialist in your area.

• Case A: Patient with melanoma diagnosed at age 53 and again at age 66 and no significant family history—no mutation was detected on Comprehensive MELARIS^®.

• Case B: Patient with melanoma at age 52 and questionable family history of skin cancer in paternal grandfather at age 72—no mutation was detected on Comprehensive MELARIS^®.

• Case C: Patient with melanoma at age 41 and mother with melanoma at age 54—no mutation was detected on Comprehensive MELARIS^®.

• Case D: Patient with melanoma at age 38 with very strong family history of melanoma and pancreatic cancer—no mutation was detected on Comprehensive MELARIS^®.

« Back to the MELARIS^® Test Results page

© 2004-06, Myriad Genetic Laboratories, Inc.