Understanding BAP1 Tumor Predisposition Syndrome
- A new study published in JAMA Dermatology suggests onychopapilloma, a benign tumor abnormality which causes thickening of one nail and a colored band along the length it, could lead to a diagnosis of a rare inherited disorder called BAP1 tumor predisposition syndrome caused by BAP1 gene mutations.
- As for BAP1 tumor predisposition syndrome, which was found in study participants who had onychopapilloma, MedlinePlus describes it as “an inherited disorder that increases the risk of a variety of cancerous (malignant) and noncancerous (benign) tumors, most commonly certain types of tumors that occur in the skin, eyes, kidneys, and the tissue that lines the chest, abdomen, and the outer surface of the internal organs (the mesothelium).
- As for what causes BAP1 tumor predisposition syndrome, it’s due mutations in the BAP1 gene.
- Our body is composed of microscopic building blocks called cells. Every cell in your body carries genetic codes that instruct your body to run properly. If there is any change or error that occurs at your gene level, your healthy cells stop working properly. These errors can lead to gene mutations, which can fuel the development of cancer.
- “One of these healthy cells is sitting put, it’s doing its job and it makes mistakes in its instructions. These instructions are called ‘DNA’, and mistakes are called ‘mutations,’” Dr. Jared Weiss, section Chief of Thoracic and Head/Neck Oncology at the University of North Carolina Lineberger Comprehensive Cancer Center, previously told SurvivorNet. “These mistakes make the cell forget how to do its job; instead it learns how to make copies of itself spread and grow, which is what cancer is.”
- According to the U.S. Centers for Disease Control and Prevention, your doctor can refer you for genetic counseling based on your personal and family health history.
The rare condition raises one’s risk of developing “cancerous tumors of the skin, eyes, kidneys and the tissue that lines the chest and abdomen,” a news release from the National Institutes of Health (NIH) explains.
Read More“His comment prompted us to systematically evaluate other participants for nail changes and uncover this new finding.”
Biopsies of study participants aged 30 and older ultimately found onychopapilloma tumors in nails and underlying nail beds, of 88% of participants, prompting researchers to suggest nail screenings could be helpful when it comes to patents with a heightened risk of melanoma or other potential BAP1-associated malignancy.
The study looked at a total of 47 participants, [30 females and 17 men from 35 families, ranging in age from 13 to 72 years. “Nail abnormalities were detected in 41 patients (87.2%) and included leukonychia, splinter hemorrhage, onychoschizia, and distal nail hyperkeratosis,” the study authors note in their findings.
“Clinical findings consistent with onychopapilloma were detected in 39 patients (83.0%), including 35 of 40 individuals aged 30 years or older (87.5%). Nail bed biopsy was performed in 5 patients and was consistent with onychopapilloma. Polydactylous involvement with onychopapillomas was detected in nearly all patients who had nail involvement (38 of 39 patients [97.4%]),” the findings state.
Edward Cowen, M.D, head of Dermatology Consultation Services at NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) also stated, “This finding is rarely seen in the general population, and we believe the presence of nail changes that suggest onychopapillomas on multiple nails should prompt consideration of a diagnosis of BAP1 tumor predisposition syndrome.
Raffit Hassan, M.D., a co-senior author of the study, added, “This discovery is an excellent example of how multidisciplinary teams and natural history studies can reveal insights about rare diseases.”
RELATED: Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome
How Genetic Testing Helps Cancer Patients
- Genetic Testing Can Empower You With Important Information
- Genetic Testing Can Help Guide Ovarian Cancer Treatment Decisions
- Considering Genetic Testing? Talk to Family if You Can
- Genetic Testing For Breast Cancer Can Be Life-Saving For Some: For Others, It Only Causes Confusion and Stress
- Getting Genetic Testing for Your Kids — a Tough, but Crucial Call
As per the study authors, “onychopapilloma is a benign tumor of the nail that presents with longitudinal leukonychia, erythronychia, or splinter hemorrhage, along with nail plate abnormalities, including longitudinal ridging, onycholysis, or V-shaped distal nicking.
“This nail condition was first described as ‘localized, distal subungual keratosis with multinucleate cells’ by Baran and Perin in 19959 and renamed onychopapilloma by the same authors in 2000. The nail abnormality typically extends linearly from the proximal nail matrix to the end of the nail, with a characteristic focal subungual keratotic papule at the hyponychium. There may be 2 bands present on the same digit, but to our knowledge, polydactylous onychopapilloma has not been previously reported in the literature.”
Understanding BAP1 Tumor Predisposition Syndrome
As for BAP1 tumor predisposition syndrome, which was found in study participants who had onychopapilloma, MedlinePlus describes it as “an inherited disorder that increases the risk of a variety of cancerous (malignant) and noncancerous (benign) tumors, most commonly certain types of tumors that occur in the skin, eyes, kidneys, and the tissue that lines the chest, abdomen, and the outer surface of the internal organs (the mesothelium).
RELATED: Understanding the Genetic Makeup of Your Tumor
“Affected individuals can develop one or more types of tumor, and affected members of the same family can have different types.”
Some patients found to have BAP1 tumor predisposition syndrome may multiple skin growths called atypical Spitz tumors, which are often benign and it’s unknown whether they can become cancerous.
Dr. Dana Chase weighs in on advocating for your health and avoiding provider bias.
MedlinePlus advises that BAP1 tumor predisposition syndrome is also linked to skin cancers, like cutaneous melanoma and basal cell carcinoma.
As for the most common cancerous tumor found in someone with this predisposition syndrome, it’s a rare type of eye cancer known as uveal melanoma.
Others with this syndrome are at risk of developing malignant mesothelioma, a rare type of cancer that arises in the thin layer of tissue covering most of a person’s internal organs [the mesothelium].
Additionally, clear renal cell carcinoma, a type of kidney cancer, is also linked to this predisposition syndrome.
As for what causes BAP1 tumor predisposition syndrome, it’s due mutations in the BAP1 gene.
MedlinePlus explains, “The BAP1 protein acts as a tumor suppressor, which means it helps prevent cells from growing and dividing too rapidly or in an uncontrolled way. Its function is to remove molecules called ubiquitin from certain proteins (deubiquitination), which can affect the activity of the protein and its interactions with other proteins. By removing ubiquitin, BAP1 helps regulate diverse cellular processes. The BAP1 protein is thought to be involved in cell growth and division (proliferation), cell death, repair of damaged DNA, and control of gene activity.
“Mutations in the BAP1 gene lead to production of an altered protein that cannot function normally and may be broken down prematurely. In addition to an inherited (germline) mutation in one copy of the gene, which is found in essentially every cell of the body, a second, non-inherited (somatic) mutation usually occurs in the normal copy of the gene in cells that give rise to tumors. Together, the germline and somatic mutations result in a complete loss of BAP1 protein function in tumor cells. A shortage of this protein’s function likely impairs the removal of ubiquitin from certain proteins.
“Although it is unclear exactly how loss of BAP1 function leads to BAP1 tumor predisposition syndrome, researchers speculate that altered activity of proteins normally regulated by BAP1 deubiquitination may promote cell proliferation or survival, resulting in tumor formation.”
The Power of Genetic Testing
Genetic tests can be as simple as a simple saliva swab or blood sample. The results help your care team determine if you have a specific mutation that puts you at higher risk for cancer.
“If someone gets a genetic test result back, it’s really important for them to know what this is. (What does this) mean for them? Put it into context,” Dr. Elisa Port, a surgical oncologist at Mount Sinai, previously explained to SurvivorNet.
Genetic Testing Can Empower You With Important Information
Genetic counselors help patients during this critical phase of understanding.
“What does it mean for their family members? For their relatives? Genetic counseling to follow up genetic testing is a really, really important part of the whole process and is not always available in the direct-to-consumer type avenue”
According to the U.S. Centers for Disease Control and Prevention, your doctor can refer you for genetic counseling based on your personal and family health history.
Genetic testing can empower you with important information and direct you to screening tests that can save your life by finding cancers even earlier, says Dr. Beth Karlan, Director of the Women’s Cancer Program at Cedars-Sinai Medical Center in Los Angeles.
“If you have a family history of cancers,” says Dr. Karlan, “you should definitely discuss with a genetic counselor or your physician whether or not you should have genetic testing.”
Basically, our body is composed of microscopic building blocks called cells. Every cell in your body carries genetic codes that instruct your body to run properly. If there is any change or error that occurs at your gene level, your healthy cells stop working properly. These errors can lead to gene mutations, which can fuel the development of cancer.
“One of these healthy cells is sitting put, it’s doing its job and it makes mistakes in its instructions. These instructions are called ‘DNA’, and mistakes are called ‘mutations,’” Dr. Jared Weiss, section Chief of Thoracic and Head/Neck Oncology at the University of North Carolina Lineberger Comprehensive Cancer Center, previously told SurvivorNet.
According to Weiss, “These mistakes make the cell forget how to do its job; instead it learns how to make copies of itself spread and grow, which is what cancer is.”
How Can Next-Generation Sequencing Help You Find a More Effective Cancer Treatment?
Researchers have found a way to examine the genetic material of a patient’s tumors. In the last few decades, they have learned a great deal about how changes in our genes can affect our health and increase the risk of cancer.
Skin Cancer Can Occur Just About Anywhere
The main types of skin cancer include basal cell carcinoma, squamous cell carcinoma, and melanoma.
In melanoma skin cancer cases, it is more likely to impact nearby tissue and spread or metastasize to other parts of the body. Melanoma also causes the most skin cancer deaths, according to the National Cancer Institute. It starts in the same cells that give your skin, hair, and eyes their color. In melanoma, the cells change in a way that allows them to spread to other organs.
Top 5 Ways to Protect Your Skin From Skin Cancer
According to SurvivorNet’s experts, changes to a mole you’ve had for a while or a new growth on your skin could be signs of melanoma. You’ll want to watch for them and tell your doctor about any changes you notice.
You’re most likely to find melanoma on sun-exposed skin areas like your face, neck, arms, and legs. Surprisingly, you might also find them in other places as well, like:
- The palms of your hands or soles of your feet
- On your eyes or mouth
- Under your nails
SurvivorNet skin cancer experts recommend avoiding unprotected sun exposure because ultraviolet (UV) radiation can lead to melanoma. Tanning beds pose ultraviolet radiation risks for skin cancer and should be avoided. Many dermatologists recommend using spray tans to reduce the risk of melanoma skin cancer.
WATCH: Examining Your Skin for Skin Cancer.
SurvivorNet’s medical experts say the most important thing to look for when finding melanoma is a new spot on your skin or a spot changing in size, shape, or color.
When you check your skin, use the acronym ABCDE as your guide. Look for:
- Asymmetrical moles: If you drew a line straight down the center of the mole, would the sides match?
- Borders: Is the mole irregular or jagged?
- Colors: Are there multiple distinct colors in the mole?
- Diameter: Is the mole larger than 6 millimeters (mm), about the size of a pencil head eraser?
- Evolution: Has the mole’s color, shape, or size changed over time?
RELATED: Myth Busting: My Fingernails Have Streaks…Do I Have Cancer?
If you answered “yes” to any of these questions, our experts say it’s time to see your dermatologist for a skin check.
Contributing: SurvivorNet Staff
Learn more about SurvivorNet's rigorous medical review process.
