Category Archives: Gene Medicine

WEDNESDAY, March 14 (HealthDay News) -- By analyzing gene mutations in patients with acute myeloid leukemia, researchers were able to more accurately predict which ones had the best chances of going into remission, and which ones would respond well to standard treatments or needed more aggressive treatment.

Doctors from Memorial Sloan-Kettering Cancer Center in New York City analyzed 18 genes from about 500 patients with acute myeloid leukemia (AML). AML is a cancer of the bone marrow, or the soft tissue that forms blood cells.

The patients had previously taken part in a clinical trial for a chemotherapy drug, daunorubicin, and researchers knew how everyone had fared in that study.

In the new analysis, the scientists used the latest gene-sequencing technology to determine what mutations were present in the cancer cells of the patients, and whether the presence of those mutations predicted how well people did.

They found that certain combinations of mutations were associated with both better or worse chances of survival, and that those genetic predictors could be used to determine whether patients would respond to the standard dose of daunorubicin or whether they should receive a higher, more aggressive dose of the drug.

Currently, some cancer hospitals already do a limited genetic analysis in leukemia patients to look for three mutations that are associated with a low or high risk of relapse, experts explained.

But about 60 percent of people fall into the intermediate category, said senior study author Dr. Ross Levine, an associate member in the Human Oncology and Pathogenesis Program at Sloan-Kettering. That leaves oncologists with a lot of uncertainty about how aggressively to treat those patients and what to tell them about their prognosis.

"If you know patients have a high chance of cure, you would pursue a standard therapeutic route," Levine said. "If you have a patient with a low chance of cure, you might consider more aggressive or investigational therapies."

Using the information from the more extensive analysis, about half of the patients who were in the intermediate risk could be put into a low- or high-risk category, Levine said.

"What we found was by studying the DNA of patients with leukemia and classifying all 500 patients, you could identify a set of mutations, which allows us to more accurately separate those at high risk of relapse, at intermediate risk of relapse and at low risk of relapse," Levine said. "Specifically, risk stratification with more extensive mutational profiling better predicts outcome than current classification schema."

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Detailed Gene Scan Might Help Guide Leukemia Treatment

Public release date: 13-Mar-2012 [ | E-mail | Share ]

Contact: Juan J. Gmez juanj.gomez@cnio.es 34-917-328-000-4060 Centro Nacional de Investigaciones Oncologicas (CNIO)

Can a gene simultaneously protect against cancer and favor its growth? Researchers at the Spanish National Cancer Research Centre have discovered a gene with this double-edged property and suspect there may be many more that share it. In the words of Oscar Fernandez Capetillo, head of the group responsible for the study, this gene "can be both Dr. Jekyll and Mr. Hyde, in that it can either protect us against the appearance of tumors or promote tumor growth".

The study, appears this week in the Journal of Experimental Medicine, with Andres J. Lopez-Contreras and Paula Gutierrez Martinez as first authors, focuses on the activity of Chk1, a gene known for its tumour suppressing effect. It is what Fernandez-Capetillo calls "a genome guardian, a gene that keeps our genome free of mutations and, therefore, protects against the development of tumours".

The team wished to ascertain whether the tumour-protective effect of Chk1 was magnified in organisms with a larger quantity of the protein it codes for, so they created a mouse with three copies of the gene instead of the normal two. They then extracted and cultured the animal's cells and turned them cancerous with the aid of other genes. What they observed confounded all expectations: the cells became malignant more easily when carrying an extra copy of Chk1.

The reason for this paradox is that Chk1 has a beneficial effect on healthy cells, but also benefits tumour cells once they have established themselves in the body.

The dual role of Chk1

"Initially, Chk1 prevents the appearance of tumours, by limiting the spontaneous mutations that take place in our cells", remarks Fernandez Capetillo. "This is the Dr. Jekyll side. However, advanced tumours exhibit extensive damage to their DNA and it is here that Chk1 comes to the tumour's aid by reducing the damage built up in its genome", he continues.

Chk1 works by protecting against replicative stress, a kind of damage that occurs in cells' genetic material as they divide. Some tumours indeed suffer continuous lesions in their genome due to their high division rates.

"The presence of 'genome guardians' like Chk1 may favour the growth of this kind of tumour by lessening its lesion load", explains Lopez-Contreras.

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CNIO researchers discover that a gene known to protect against cancer can also promote tumor growth

Washington, March 14 (ANI): A gene that can simultaneously protect against cancer and favour its growth has been identified.

Researchers at the Spanish National Cancer Research Centre who made the discovery suspect there may be many more genes that share this double-edged property.

In the words of Oscar Fernandez Capetillo, head of the group responsible for the study, this gene "can be both Dr. Jekyll and Mr. Hyde, in that it can either protect us against the appearance of tumours or promote tumour growth".

The study co-authored by Andre's J. Lopez-Contreras and Paula Gutierrez Martinez, focuses on the activity of Chk1, a gene known for its tumour suppressing effect.

It is what Fernandez-Capetillo calls "a genome guardian, a gene that keeps our genome free of mutations and, therefore, protects against the development of tumours".

The team wished to ascertain whether the tumour-protective effect of Chk1 was magnified in organisms with a larger quantity of the protein it codes for, so they created a mouse with three copies of the gene instead of the normal two.

They then extracted and cultured the animal's cells and turned them cancerous with the aid of other genes. What they observed confounded all expectations: the cells became malignant more easily when carrying an extra copy of Chk1.

The reason for this paradox is that Chk1 has a beneficial effect on healthy cells, but also benefits tumour cells once they have established themselves in the body.

"Initially, Chk1 prevents the appearance of tumours, by limiting the spontaneous mutations that take place in our cells," explained Fernandez Capetillo.

"This is the Dr. Jekyll side. However, advanced tumours exhibit extensive damage to their DNA and it is here that Chk1 comes to the tumour's aid by reducing the damage built up in its genome," he said.

Read this article:
Gene known to protect against cancer can also promote tumour growth

ScienceDaily (Mar. 13, 2012) Can a gene simultaneously protect against cancer and favor its growth? Researchers at the Spanish National Cancer Research Centre have discovered a gene with this double-edged property and suspect there may be many more that share it. In the words of Oscar Fernandez Capetillo, head of the group responsible for the study, this gene "can be both Dr. Jekyll and Mr. Hyde, in that it can either protect us against the appearance of tumors or promote tumor growth."

The study, appears this week in the Journal of Experimental Medicine, with Andres J. Lopez-Contreras and Paula Gutierrez Martinez as first authors, focuses on the activity of Chk1, a gene known for its tumour suppressing effect. It is what Fernandez-Capetillo calls "a genome guardian, a gene that keeps our genome free of mutations and, therefore, protects against the development of tumours."

The team wished to ascertain whether the tumour-protective effect of Chk1 was magnified in organisms with a larger quantity of the protein it codes for, so they created a mouse with three copies of the gene instead of the normal two. They then extracted and cultured the animal's cells and turned them cancerous with the aid of other genes. What they observed confounded all expectations: the cells became malignant more easily when carrying an extra copy of Chk1.

The reason for this paradox is that Chk1 has a beneficial effect on healthy cells, but also benefits tumour cells once they have established themselves in the body.

The dual role of Chk1

"Initially, Chk1 prevents the appearance of tumours, by limiting the spontaneous mutations that take place in our cells," remarks Fernandez Capetillo. "This is the Dr. Jekyll side. However, advanced tumours exhibit extensive damage to their DNA and it is here that Chk1 comes to the tumour's aid by reducing the damage built up in its genome," he continues.

Chk1 works by protecting against replicative stress, a kind of damage that occurs in cells' genetic material as they divide. Some tumours indeed suffer continuous lesions in their genome due to their high division rates.

"The presence of 'genome guardians' like Chk1 may favour the growth of this kind of tumour by lessening its lesion load," explains Lopez-Contreras.

"This study sheds light on why Chk1 is overexpressed in many tumours, when we would intuitively suppose that what favours the development of cancer is the loss of protective genes," the scientist concludes.

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Gene known to protect against cancer can also promote tumor growth

MEMPHIS, Tenn., March 13, 2012 /PRNewswire/ --Researchers have identified the first gene mutation associated with a chronic and often fatal form of neuroblastoma that typically strikes adolescents and young adults. The finding provides the first clue about the genetic basis of the long-recognized but poorly understood link between treatment outcome and age at diagnosis.

To view the multimedia assets associated with this release, please click: http://www.multivu.com/mnr/52992-st-jude-pediatric-cancer-genome-project-neuroblastoma-research

The study involved 104 infants, children and young adults with advanced neuroblastoma, a cancer of the sympathetic nervous system. Investigators discovered the ATRX gene was mutated only in patients age 5 and older. The alterations occurred most often in patients age 12 and older. These older patients were also more likely than their younger counterparts to have a chronic form of neuroblastoma and die years after their disease is diagnosed.

The findings suggest that ATRX mutations might represent a new subtype of neuroblastoma that is more common in older children and young adults. The work is from the St. Jude Children's Research Hospital Washington University Pediatric Cancer Genome Project (PCGP). The study appears in the March 14 edition of the Journal of the American Medical Association.

If validated, the results may change the way doctors think about this cancer, said co-author Richard Wilson, Ph.D., director of The Genome Institute at Washington University School of Medicine in St. Louis. "This suggests we may need to think about different treatment strategies for patients depending on whether or not they have the ATRX mutation," he said.

Neuroblastoma accounts for 7 to 10 percent of all childhood cancers and about 15 percent of pediatric cancer deaths. In about 50 percent of patients, the disease has already spread when the cancer is discovered.

For patients whose disease has spread, age has long been a powerful but perplexing predictor of treatment outcome. Currently 88 percent of patients age 18 months and younger become long-term survivors, compared to 49 percent of those ages 18 months through 11 years and only 10 percent of patients age 12 and older.

"Until now there was no understanding of the basis of this age-related risk, and no treatment has had an impact on the outcome," said Michael Dyer, Ph.D., a member of the St. Jude Department of Developmental Neurobiology and a Howard Hughes Medical Institute Early Career Scientist. He is the study's corresponding author. "The mutation we found is associated with patients in the older age group, but it also identifies for the first time a subset of younger patients who turned out to have an indolent form of neuroblastoma."

Researchers must now determine whether tumors with ATRX mutations behave the same way in both children and young adults, following a similarly indolent but often deadly course, said Nai-Kong Cheung, M.D., Ph.D., first author and head of the Neuroblastoma Program at New York's Memorial Sloan-Kettering Cancer Center.

St. Jude investigators have begun screening the hospital's library of federally approved drugs looking for evidence of activity against neuroblastoma cells with the ATRX mutation. Availability of more targeted therapies would likely spur efforts for early identification of patients with the ATRX mutation who have a chronic form of neuroblastoma and are unlikely to benefit from current therapies.

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Genome Sequencing Initiative Links Altered Gene to Age-Related Neuroblastoma Risk

Published: March. 12, 2012 at 9:30 PM

LOS ANGELES, March 12 (UPI) -- U.S. scientists say they've identified, for the first time, a way to fix mutations in human DNA, a finding with implications for treating a host of diseases.

Currently, there is no way to successfully repair or compensate for these mutations in the human mitochondrial genome, implicated in neuromuscular diseases, metabolic defects and aging, researchers at UCLA said.

Scientists at the UCLA stem cell center, and the departments of chemistry and biochemistry and pathology and laboratory medicine, said targeting corrective, or messenger RNAs may correct mutations in human mitochondrial DNA.

RNA molecules play an active role in cells by catalyzing biological reactions, controlling gene expression and directing the synthesis of proteins.

"I think this is a finding that could change the field," Dr. Michael Teitell, a professor of pathology and laboratory medicine, said. "We've been looking to do this for a long time and we had a very reasoned approach, but some key steps were missing.

"Now we have developed this method and the next step is to show that what we can do in human cell lines with mutant mitochondria can translate into animal models and, ultimately, into humans."

Mitochondria generate most of the energy supply within a cell and are also are involved in other cellular processes, including signaling, differentiation, death, control of the cell cycle and growth, the researchers said.

The findings could lead to a form of gene therapy by compensating for mutations that cause a wide range of diseases, study co-senior author Koehler.

"This opens up new avenues to understand and develop therapies for mitochondrial diseases," researcher Carla Koehler said. "This has the potential to have a really big impact."

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DNA finding could mean new gene therapies