Health Scan: Newly discovered gene affects melanoma survival

Gene is a newly identified member of a group of genes called tumor suppressor genes.

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November 8, 2015 01:13
4 minute read.
Petri dish [Illustrative]

Petri dish [Illustrative]. (photo credit: REUTERS)

 
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Of the hundreds of genes that can be mutated in a single case of melanoma, only a handful may be true “drivers” of cancer. In research that recently appeared in Nature Genetics, a Weizmann Institute of Science team has now revealed one of the drivers of a particularly deadly subset of melanomas – one that is still seeing a rise in new cases.

This gene is a newly identified member of a group of genes called tumor suppressor genes. It is mutated in some 5.4 percent of melanomas.

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Furthermore, its expression was found to be lost in over 30% of human melanomas, and this loss, according to the finding, was associated with reduced patient survival.

This discovery might open new doors to understanding how this cancer grows and spreads and lead in the future to new directions in treating this disease, said Prof. Yardena Samuels and her team in the institute’s molecular cell biology department. They were specifically searching for tumor suppressor genes in their database, which consists of more than 500 melanoma genomes and exomes – protein-building sequences – making it the largest melanoma dataset to date.

Tumor suppressor genes normally inhibit cell growth, including that of cancer cells, but when mutated, they act like defective brakes on cellular proliferation. Thus studying these genes is crucial in cancer biology.

“The identification of targetable alterations in melanoma is an urgent need. An in-depth understanding of the functional effects of mutations in these genes is the first step toward revealing the underlying mechanism of melanoma growth,” said Dr. Nouar Qutob, a postdoctoral fellow in Samuels’ lab who participated in this research.

Indeed, the melanoma genome sequences contained mutations in known tumor suppressor genes, but there was also a new gene that stood out in the team’s search, named RASA2. The researchers found that RASA2 regulates a key protein in the cell, called RAS. RAS has been identified as a major oncogene that contributes to the unchecked growth of cells. When they restored the production of the protein in melanoma cells that harbored RASA2 mutations, these cells stopped growing and eventually died.



Patients with dysfunctional RAS pathways tend to have a worse prognosis than those with other types of melanoma, and, until now, scientists have not managed to create drugs that can target this pathway. Most targeted cancer therapies nowadays work by inhibiting the products of oncogenes that are overactive in melanoma cells.

However, loss or mutations in tumor suppressor genes like RASA2 also contribute to melanoma development.

DA VINCI TO THE RESCUE

In a rare operation performed only a few times before in the world, Rambam Medical Center surgeons recently used a robot to remove a rare and life-threatening potato- sized benign growth from the throat of a 59-year-old Haifa man. The patient, who had considered living permanently with a hole in his trachea before the operation was carried out, was restored to normal life by the procedure.

The growth greatly disrupted his ability to breathe and eat, and at night, when he tried to sleep, it closed his trachea and caused him to choke. He was unable to sleep normally and continuously for two years.

According to Rambam, where he applied for help after fruitlessly trying to get effective treatment in several hospitals, anesthesiologists elsewhere were unable to insert a breathing tube into his trachea. Prof. Ziv Gil, head of the ear-nose-and-throat and head and throat surgery at Rambam and Dr. Yaki Cohen, head of the hearing and speech institute decided to try a da Vinci robot on the patient.

The two-hour operation was carried out only via the mouth, without incisions in the throat. Using a tiny 3D camera and two robotic arms, they managed to remove the tumor without injuring the man’s vocal cords or trachea.

The patient was released two days later breathing normally for the first time in years.

DOGS CALM KIDS WITH CANCER

Although survival rates for children diagnosed with cancer have increased dramatically over the past four decades, hard evidence of proven methods to improve quality of life among patients and families during treatment has remained elusive.

Many hospitals have “therapy dogs” who visit with patients, and anecdotal evidence underscores the positive impact these programs have on children with cancer and their families. Preliminary findings from a new, multi-center trial provides some of the first quantitative data to validate these claims.

The study, presented at the American Academy of Pediatrics national conference in Washington, collected data on blood pressure, pulse rates and anxiety levels of children before and after a weekly visit from a therapy dog.

During the visits, children pet or talk to the dog, brush its fur, view the dog’s photos, watch the dog practicing tricks or commands and learn about various breeds.

Preliminary findings show that blood pressure readings in the group receiving animal-assisted interventions remains more stable across all sessions than in the control group, said lead researcher Dr. Amy McCullough of the American Humane Association. Similarly, there was a higher degree of variability in heart rate within the control group patients than with the treatment group patients.

The national, multi-site study is the first of its kind to rigorously measure the psychosocial effects of the encounters, McCullough said. So far, 68 children aged three to 17 and newly diagnosed with cancer have been enrolled in the study. In addition to the effects on pulse and heart rate to date, preliminary results indicate the canine encounters appear to improve anxiety levels among parents. Overall, children in both groups showed a decrease in anxiety over the course of their study enrollment. The findings are expected to further increase access to therapy animals in hospital environments, enhance therapy dog training and practice and improve well-being outcomes for children and families facing the challenges of childhood cancer, she said.

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