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The Partnership to Reduce Cancer in Rhode Island, 2017. Proudly created with


Scientists Identify Genes Tied to Increased Risk of Ovarian Cancer

Medically reviewed by Alexander Gusev, PhD

August 14, 2019

A team of Dana-Farber scientists and their associates has identified 34 genes associated with an increased risk of developing earliest-stage ovarian cancer. The findings, published in the journal Nature Genetics, will both help identify women who have the highest risk of developing ovarian cancer and pave the way for identifying new therapies that can target these genes.

Currently, there is no effective screening test for ovarian cancer and the disease is notorious for being detected in later stages when survival rates are poor. However, if ovarian cancer is caught early, survival rates increase dramatically, underscoring the need to identify those who may be at risk for developing the disease.

The study, led by Dana-Farber’s Alexander Gusev, PhD, Simon Gayther, PhD, of Cedars-Sinai Medical Center in Los Angeles, and Bogdan Pasaniuc, PhD, of the University of California at Los Angeles, drew on genetic data gathered over more than a decade by the Ovarian Cancer Association Consortium. The researchers compared the genetic profiles of about 25,000 women with ovarian cancer and 45,000 women without the disease and found more than 30 regions of the genome associated with ovarian cancer.


The next task was to pick out the specific genes within those regions that are responsible for the increase in ovarian cancer risk.


“The main challenge has to do with the number of genes that are in one region of the genome,” explains Pasaniuc. “Whenever you inherit a piece of DNA from your parents, you don’t inherit just every base pair of the genome, you inherit big chunks. That means that if you inherit a gene mutation in a given region, you inherit the entire region, which can carry 10 to 20 genes at a time. This makes it very hard to pinpoint specific genes from specific regions.”

Detective work

The team compared the large-scale genetic data from the Ovarian Cancer Association Consortium with data on mutations that disrupt the genes in ovarian and other tissues. By putting these two pieces of information together, the researchers were able to identify 34 genes associated with an increased risk of developing ovarian cancer.

The study discovered that in women at greatest risk of ovarian cancer because of their genetic blueprint, “there is an interplay between their genetics and the specific genes that drive the very earliest stages of cancer development,” said Gayther. Ultimately, the findings may provide a basis for stratifying women based on their likelihood of developing the disease.


“One novelty of this work is that we looked at risk variants that operate through alternative splicing rather than just the total abundance of a gene, which led us to genes we would not have otherwise identified,” Gusev observes. “Beyond a better understanding, mechanisms that operate through splicing open up new drug-target opportunities.”

Melanoma: What It Is, How to Spot It, and Treatment Options

Medically reviewed by F. Stephen Hodi, MD

August 5, 2019

Melanoma is a rare but aggressive form of skin cancer that originates in melanocytes, the cells that create pigment (melanin) to protect us from ultraviolet (UV) radiation.


Melanoma is categorized into one of three subtypes, depending on its location:

  • Cutaneous melanoma: Melanoma of the skin. Common affected areas include the face, neck, hands, and arms, all of which are often exposed to sunlight.

  • Mucosal melanoma: Melanoma that occurs in a mucous membrane, including the throat, nasal passages, or the mouth.  

  • Ocular or uveal melanoma: A rare form of the disease that originates in the uvea, the pigmented layer of the eye. 


Not all skin cancers are melanoma, and while the disease is aggressive, it’s also quite rare: according to the American Cancer Society, melanoma accounts for 1% of all skin cancers.

What causes melanoma?

Exposure to ultraviolet (UV) rays is a major risk factor for melanoma. UV rays are present in sunlight and are also produced by artificial sources such as tanning beds. UV rays are hazardous because they damage the DNA of skin cells; when the genes controlling cell growth are affected by this damage, cancer can develop.


There are steps you can take to combat UV damage, including:

  • Applying sunscreen (a minimum SPF of 30)

  • Seeking shade when possible

  • Covering up with sunglasses, clothing, and a hat


If you have additional questions, be sure to meet with a dermatologist; your primary care physician should be able to refer you to someone. Dermatologists can provide screenings, offer advice, and identify moles that may require a biopsy.


People with fair skin, multiple freckles, and light hair have a higher risk of developing melanoma, due to the fact they are more likely to get sunburnt. In fact, studies indicate Caucasians are 20 times more likely to be diagnosed with melanoma than African Americans.    


Other risk/contributing factors to melanoma include:

  • Family history

  • A blistering sunburn, even a single sun burn can damage skin cells

  • Age — while melanoma is more prevalent in older individuals, it is becoming one of the most common cancers in young adults.  

How to spot melanoma


Melanoma can occur anywhere on the body, and it’s important for individuals to do a monthly self-exam to spot areas of concern. Stephen Hodi, MD, the Director for the Center of Melanoma Oncology at Dana-Farber/Brigham and Women’s Cancer Center, encourages people to make an appointment with a dermatologist if they find anything new or concerning. Dermatologists can use a dermascope, a tool that combines a flashlight with a microscope, to spot potentially dangerous moles.


“Early detection and surgical removal is still the best treatment,” explains Hodi. “Make sure to work with your primary care physician to determine how often you need to be screened.”


Typically, a normal mole is evenly colored (brown, tan, or black), can be either flat or raised, and is less than 6 millimeters across (the size of a pencil eraser). A benign mole, whether it’s present at birth or develops over time, will usually stay the same size, shape, and color. If a mole does not fit this description, it’s important to have it examined.


In doing your self-examination, consider your ABCDEs:

  • Asymmetry: Is the mole asymmetrical? Does one half of the mole look different than the other?

  • Border: Are the edges of the mole irregular, jagged, or blurred?

  • Color: Does the mole include shades of brown or black, or patches of pink, white, red, or blue?

  • Diameter: Is the mole larger than six millimeters across?

  • Evolving: Is the mole changing in size, shape, or color?


If the answer to any of these questions is yes, consult your primary care physician or dermatologist. Your dermatologist may even photograph your moles to better track them over time.


Other warning signs include moles that itch, bleed, or become ulcerated – a portion of the skin that covers the mole is broken.


Remember, not all melanomas fit the rules of the ABCDEs; some melanomas can be smaller than six millimeters, for example.


While most moles are harmless, it’s important to be vigilant and contact a dermatologist if you have any concerns.

How is melanoma diagnosed?


A biopsy is needed to confirm a melanoma diagnosis. If you are diagnosed with melanoma, it will fall into one of five stages.

  • Stage 0: At stage 0, the cancer is confined to the epidermis, or the outermost layer of the skin.

  • Stage I: Stage I melanoma is no more than 2 millimeters (mm) thick. It is considered to be a localized tumor and has not spread to the surrounding lymph nodes or distant sites.  

  • Stage II: Stage II melanoma is defined by its thickness, ranging from 1-4 millimeters thick. This stage of melanoma is considered more likely to metastasize but has not spread to surrounding lymph nodes or distant sites at the time of diagnosis.

  • Stage III: Stage III melanoma is known as regional melanoma, and it is disease that has spread to nearby lymph nodes, lymph vessels, or the skin.

  • Stage IV: Stage IV melanoma is disease that has metastasized to other parts of the body, including the brain, lungs, or liver.

Treatment options for melanoma


Treatments for a melanoma diagnosis will depend on the stage of the disease. Surgical removal of the tumor is still the most effective treatment and is typically all that is required for stages 0-2. The surgery will include removal of the tumor as well as surrounding normal tissue to decrease the chance of a local recurrence. The surgeon may also perform a sentinel lymph node biopsy. This procedure removes and tests the first lymph node the cancer is likely to spread to.


Following surgery, some patients may receive adjuvant therapy. Adjuvant therapies are treatments that lower the risk of the cancer returning. For melanoma patients, this can range from chemotherapy to targeted and immunotherapy.


For patients whose cancer has metastasized, your oncologist will look to deliver systemic therapy (drugs spread throughout the body to treat cancer cells where they are) following surgery. In the last decade, there have been numerous advancements in treatment options for metastatic and high-risk melanoma.


Today, patients have the option for both immunotherapy as well as targeted therapy. Immunotherapy drugs for melanoma patients primarily act as either a PD-1 or CTLA-4 inhibitor, and patients may receive either a single agent or a combination of both. By preventing PD-1 and/or CTLA-4 from activating, the body’s immune system is given a boost in its ability to detect and target cancer cells. Immunotherapy is typically the first line of treatment for metastatic melanoma; however, depending on the circumstances, an oncologist may initially utilize targeted therapy.


The goal of targeted therapy is to shut down the cells responsible for cancer growth without harming the

surrounding healthy tissue. For melanoma patients, targeted therapies are currently only available for those with a BRAF mutation – a mutation found in roughly half of all melanoma tumors. Today’s targeted therapy drugs are aimed at shutting down BRAF and MEK proteins, both of which play a role in cancer cell growth.

Latest research


By studying melanoma tumors, researchers hope to find new targetable molecular mechanisms that can improve survival rates for more patients.


“Immunotherapy has been a game changer,” explains Hodi. “The goal now is to continue to explore effective options that can turn this into a chronic illness.”


In addition to numerous ongoing clinical trials, researchers are also exploring the use of melanoma vaccines. These vaccines won’t prevent melanoma, but researchers hope they may be able to utilize them to either delay or possibly prevent a recurrence.


One of the issues critical to improving outcomes for people with ovarian cancer is early detection and screening. Currently, genetic testing is a reimbursable service but genetic counseling, a key component of the early detection screening process, is not unless a physician is present. The Partnership is pleased to support legislation drafted by Paul A. DiSilvestro, MD, Director of the Program in Women’s Oncology and Women & Infants Hospital which would establish a licensure program for genetic counselors. This would increase access to this service by allowing genetic counselors to work independently and receive reimbursement without a physician present.