Scientists have identified a striking signature in tumour DNA that occurs in five different types of cancer. They also found evidence that this methylation signature may be present in many more types of cancer. Middle East Health reports.
US National Institutes of Health researchers have found a specific gene signature in cancer tissue that results from a chemical modification of DNA called methylation, which can control the expression of genes like a dimmer on a light switch. Higher amounts of DNA methylation (hypermethylation), like that found by the researchers in some tumour DNA, decreases a gene's activity. Based on this advance, the researchers hope to spur development of a blood test that can be used to diagnose a variety of cancers at early stages, when treatments can be most effective. The study appeared in the 5 February 2016 issue of The Journal of Molecular Diagnostics.
"Finding a distinctive methylationbased signature is like looking for a spruce tree in a pine forest," said Laura Elnitski, Ph.D., a computational biologist in the Division of Intramural Research at NIH's National Human Genome Research Institute (NHGRI). "It's a technical challenge to identify, but we found an elevated methylation signature around the gene known as ZNF154 that is unique to tumours. "Dr Elnitski is head of the Genomic Functional Analysis Section and senior investigator in the Translational and Functional Genomics Branch at NHGRI.
In 2013, her research group discovered a methylation mark (or signature) around ZNF154 in 15 tumour types in 13 different organs and deemed it a possible universal cancer biomarker. Biomarkers are biological molecules that indicate the presence of disease. Dr Elnitski's group identified the methylation mark using DNA taken from solid tumours.
"No one in my group slept the night after that discovery," Dr Elnitski said. "We were so excited when we found this candidate biomarker. It's the first of its kind to apply to so many types of cancer."
In this new study, they developed a series of steps that uncovered telltale methylation marks in colon, lung, breast, stomach and endometrial cancers. They showed that all the tumour types and subtypes consistently produced the same methylation mark around ZNF154.
"Finding the methylation signature was an incredibly arduous and valuable process," said NHGRI Scientific Director Dan Kastner, M.D., Ph.D. "These findings could be an important step in developing a test to identify early cancers through a blood test."
The NIH Intramural Sequencing Center sequenced the tumour DNA that had been amplified using a technique called polymerase chain reaction (PCR). Dr Elnitski and her group then analyzed the results, finding elevated levels of methylation at ZNF154 across the different tumour types.
To verify the connection between increased methylation and cancer, Dr Elnitski's group developed a computer program that looked at the methylation marks in the DNA of people with and without cancer. By feeding this information into the program, they were able to predict a threshold for detecting tumour DNA. Even when they reduced the amount of methylated molecules by 99%, the computer could still detect the cancer-related methylation marks in the mixture. Knowing that tumours often shed DNA into the bloodstream, they calculated the proportions of circulating tumour DNA that could be found in the blood.
Screening blood samples
Dr Elnitski will next begin screening blood samples from patients with bladder, breast, colon, pancreatic and prostate cancers to determine the accuracy of detection at low levels of circulating DNA. Tumour DNA in a person with cancer typically comprises between 1 and 10% of all DNA circulating in the bloodstream. The group noted that when 10% of the circulating DNA contains the tumour signature, their detection rate is quite good. Because the methylation could be detected at such low levels, it should be adequate to detect advanced cancer as well as some intermediate and early tumours, depending on the type.
Dr Elnitski's group will also collaborate with Christina Annunziata, M.D., Ph.D., an investigator in the Women's Malignancies Branch and head of the Translational Genomics Section at NIH's National Cancer Institute (NCI). They will test blood samples from women with ovarian cancer to validate the process over the course of treatment and to determine if this type of analysis leads to improved detection of a recurrence and, ultimately, improved outcomes.
"Ovarian cancer is difficult to detect in its early stages, and there are no proven early detection methods," said Dr Annunziata. "We need a reliable biomarker for detecting the disease when a cure is more likely. We are looking forward to testing Dr Elnitski's novel approach using DNA methylation signatures."
Current blood tests are specific to a known tumour type. In other words, clinicians must first find the tumour, remove a sample of it and determine its genome sequence. Once the tumour-specific mutations are known, they can be tracked for appearance in the blood. The potential of the new approach is that no prior knowledge of cancer is required, it would be less intrusive than other screening approaches like colonoscopies and mammograms and it could be used to follow individuals at high risk for cancer or to monitor the activity of a tumour during treatment. Once the blood test is developed, the scientific community must conduct studies to ensure that it does not indicate the presence of cancer when it is not there or miss cancer when it is there.
Dr Elnitski does not yet understand the connection between tumours and elevated DNA methylation. It may represent derailment of normal processes in the cell, or it may have something to do with the fact that tumours consume a lot of energy and circumvent the cellular processes that keep growth in check. Researchers also don't know exactly what the gene ZNF154 does. "We have laid the groundwork for developing a diagnostic test, which offers the hope of catching cancer earlier and dramatically improving the survival rate of people with many types of cancer," Dr Elnitski said.
WORLD CANCER DAY
Middle East forecast to have highest growth of cancer in the world over next 20 years To mark World Cancer Day on 4 February, the WHO Eastern Mediterranean Regional office issued a statement saying 400,000 people, young and old, die every year in the Region due to cancer.
On World Cancer Day, under the slogan "We Can. I Can.", WHO called on governments to provide and improve access to quality cancer care and on communities and individuals to quit smoking, eat healthy food and keep active.
Cancer is one of the world's biggest killers and ranks among the top 4 leading causes of death in the Region, yet is a preventable disease.
"Regrettably," says Dr Ala Alwan, WHO Regional Director for the Eastern Mediterranean, "evidence shows that cancer rates continue to rise globally and regionally because of unhealthy lifestyles and limited access to treatment and quality cancer care."
In the next 20 years, cancer rates in the Region are expected to almost double, from an estimated 555,318 new cases in 2012 to nearly 961,098 in 2030 - the highest relative increase among all WHO regions. "There is a pressing need to take action to reverse this trend," said Dr Ala Alwan.
More than 30% of cancers can be prevented through the adoption of healthy lifestyles. Raising people's awareness of the links between lifestyle and cancer will empower people to make healthy lifestyle choices, such as quitting smoking, keeping physically active and eating healthy food and can also reduce the cancer burden.
There are serious gaps in access to treatment and quality cancer care in many countries of this Region. "Health systems need to be strengthened by moving towards universal health coverage which means ensuring health care services to all people at affordable costs," explains Dr Alwan.
Cancer is one of the main noncommunicable diseases that kill more than 2.2 million people in the Region every year. Cancer prevention and control are possible but require action on all fronts.
The regional framework for action, a road map for
countries of the Region to implement the United Nations Political Declaration
on Prevention and Control of Noncommunicable Diseases, is central to accelerating
action on cancer prevention and control. It sets out some of the strategic
milestones that countries need to reach if they are to achieve the 9 voluntary
targets to reduce the number of premature deaths from noncommunicable
diseases by 25% by 2025. The targets address risk behaviours, such as
tobacco use, harmful use of alcohol, unhealthy diet and physical inactivity.
AUBMC facility leads the way in cancer treatment
The Naef K. Basile Cancer Institute (NKBCI) at American University of Beirut Medical Center (AUBMC) is a state-of-the-art adult cancer facility that provides comprehensive cancer treatment and research.
This Center of Excellence became operational through a generous contribution by the Naef K. Basile Foundation (NBF) established in 1995 following the death of Dr. Naef Basile, a Lebanese-American obstetrician-gynecologist whose lifelong wish was to give back to his country of birth through the establishment of the NKBCI. He wanted to establish an institute with a vision to be the leading institute for cancer prevention and treatment through promoting excellence in patient care, research, and education, enhancing the effectiveness and collaboration among cancer programs and health care providers.
NKBCI is dedicated to the treatment of adult cancer patients (over 2500 new patients annually). It is the first in Lebanon to develop subspecialized programs for the management of brain, breast, gastrointestinal, genitourinary, head and neck and lung cancers, in addition to lymphoma, hematological malignancies, bleeding and thrombotic disorders, and Stem Cell Transplantation. At NKBCI we performed the first unrelated donor stem cell transplant in Lebanon, and over 100 stem cell transplants are done annually. The Radiation Therapy team at NKBCI at AUBMC has also performed the first radiofrequency ablation of a breast mass in Lebanon. NKBCI established the first Cancer Prevention and Control Program in Lebanon in addition to the Palliative Care Service. It is the first in Lebanon to have specialized oncology nurses (AUBMC is the first healthcare facility with MAGNET designation in the Middle East Region), case managers, social workers and dedicated oncology pharmacists as part of the multidisciplinary team. NKBCI has a leading fellowship training Program with strong affiliations with regional and international institutions including King Faisal Specialist Hospital and Research Center, King Hussein Cancer Center, MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, and the Winship Cancer Institute. NKBCI has established the first structured Data Management and Clinical Research Unit in Lebanon with a prospective database for several cancer disease sites. Our faculty are national, regional, and international leaders in clinical and translational research with ongoing clinical trials and more than 70 major publications annually.
Physician group issues advice, raises questions about Best Practices for evaluating blood in the urine as a sign of cancer
Physician group issues advice, raises questions about Best Practices for evaluating blood in the urine as a sign of cancer In some patients, blood in the urine, or hematuria, may be the only warning sign of cancer in the urinary tract. A new report from the American College of Physicians' High Value Care Task Force issues advice for physicians on how to detect and evaluate hematuria. The report, which was first-authored by a UNC Lineberger Comprehensive Cancer Center member, also raises questions around potential harms associated with diagnostic tests that are commonly employed to evaluate this condition.
"Blood in the urine can have many causes, and may be associated with urinary tract cancers including bladder cancer and cancer of the upper urinary tract," said Matt Nielsen, MD, MS, a UNC Lineberger member, co-director of the Multidisciplinary Urologic Oncology Program and associate professor of urology in the UNC School of Medicine. "But, given how common this finding is in clinical practice, we need to ensure that follow-up testing is done in a way that properly balances all of the potential harms and benefits of testing."
There is little controversy surrounding evaluation of patients with gross hematuria, which is blood in the urine visible to the naked eye, the paper reports. The ACP advises that all adults with gross hematuria should be referred for further urologic evaluation, even if the symptoms have stopped, given the relatively high risk this symptom has for underlying cancer.
More commonly, patients may have a small amount of blood in the urine that is discovered only through testing. The cancer risk is lower for microscopic hematuria than that associated with gross hematuria, and there is a lack of clarity regarding indications for specific diagnostic testing strategies for individual patients, Nielsen said.
For suspicion of hematuria raised based on the findings of what is known as a "dip-stick" test, the ACP advises that physicians confirm that finding using a microscope before further evaluation.
Physicians should consider referring adults with microscopically confirmed hematuria for evaluation by a urologist using cystoscopy and imaging in the absence of another possible, demonstrable and benign cause for it, the report suggests. However, they also pointed to the potential harms associated with cystoscopy - anxiety, discomfort and possible infection from endoscopic evaluation of the bladder - as well as potential harms linked to CT imaging.
They point to the increasing recognition of potential
longer-term harms of imaging given the evidence linking radiation doses
associated with CT scans to increased cancer risk. Acknowledging that
the association between radiation exposure from CT imaging and lifetime
cancer risk has only been indirectly estimated, they call for further
scrutiny of the issue.
University of Chicago Medicine offers minimally invasive surgery to successfully treat lung cancer
In the treatment of lung cancer, an experienced hand coupled with the help of technology can greatly improve patient outcomes
At the University of Chicago Medicine, several minimally invasive options are offered for treatment, overseen by experienced and dedicated thoracic surgeons. Despite tremendous advances in cancer care, lung cancer remains one of the deadliest forms of cancer in the world. Lung cancer, including non-small cell lung cancer (NSCLC), is the leading cause of cancer- related death. In fact, more people die from lung cancer than from colon, breast and prostate cancers combined, according to the American Cancer Society.
At the University of Chicago Medicine, Dr Christopher H. Wigfield, Associate Professor of Surgery, is an expert in adult thoracic surgery and lung transplantation. As Surgical Director of the Lung Transplant Program, Dr Wigfield cares for patients with a wide range of cardiothoracic diseases, including lung cancer. In addition, his clinical research focuses on lung transplantation and robotic assisted thoracic innovation.
“Innovation in minimally invasive surgery has allowed for an easier patient recovery process. Whenever possible, it is preferred to use minimally invasive techniques to prevent excessive bleeding and pain post-surgery,” said Dr Wigfield. “At the University of Chicago Medicine, we offer a well-trained team with experience to perform such procedures when appropriate. Our first priority is the safety and comfort of our patients that come to us.”
Innovations in minimally invasive surgery
Almost two decades ago, the initiation of minimally invasive surgery (http://www. uchospitals.edu/specialties/minisurgery/index. html) has revolutionized the surgical care experience. Patients experience less bleeding and pain as well as shorter hospital stays and can return to their lives after just a few days, a welcome improvement compared to open procedures that require long recovery periods in the hospital. All of the following procedures are primarily available only at leading academic hospitals – such as the University of Chicago Medicine.
In surgical lung oncology, surgeons commonly utilize video-assisted thoracic surgery (VATS) to perform resections, lobectomies or other types of surgeries.
This minimally invasive technique requires only three small incisions. During the procedure, a surgeon can remove a cancerous part of the lung through an incision less than two inches long.
Due to rapidly evolving technological advances in robotic surgery, thoracic surgeons at the University of Chicago Medicine now perform robot-assisted lung resection and other thoracic procedures. This approach uses computer-aided technology and robotics to provide surgeons a greater range of motion, high-definition three-dimensional views and fine precision while operating within the chest cavity. Like the VATS procedure, robotic surgery requires only a few small incisions.
And, finally, the latest treatments for lung cancer are medicines that interfere with the growth and spread of cancer cells. Called targeted therapies, these medicines are used along with chemotherapy and radiation.
Barbara Arvia is grateful for the bunion on her foot. Preparation for foot surgery led to a surprising diagnosis of lung cancer – and to state-of-the-art treatment at the University of Chicago Medicine.
Barbara considers herself lucky because her cancer was found early. Early detection and early treatment offer the best opportunity to fully eliminate any cancer. In addition, given that her lung cancer was at an early stage, she was an ideal patient for VATS.
“VATS is an option for most small or peripheral lung tumours,” says Dr Mark Ferguson, MD, a University of Chicago thoracic surgeon who specializes in surgery of the lung and oesophagus, including minimally invasive surgery for lung cancer.
It offers the best results with patients who have not undergone pre-operative chemotherapy or radiation therapy.
Barbara looks back: “Learning I had lung cancer, I was terrified. But Dr Ferguson’s team and everyone I had contact with at the University of Chicago Medicine were wonderful and tried to make me feel comfortable.” She adds: “I feel blessed. I think sometimes you’re guided to the right people and I was.”
UCM brings robots into the surgical room
Experts have different opinions on whether one minimally invasive technique is superior to other traditional methods, and it will be a point of contention for some time.
Improvements in technology have offered more versatile and precise systems. For example, the da Vinci robotic-assisted surgery system provides a 3-D view of the patient’s anatomy and ergonomic “wristed” instruments for improved magnification, allowing greater freedom of movement and precision. Although robotic surgery has found widespread utility across many surgical specialties, robotassisted thoracic surgery is still considered a novel approach.
In a study recently published in the Annals of Thoracic Surgery, researchers compared the outcomes of more than 33,000 lung cancer patients. As part of their study, the researchers conducted a propensitymatched analysis to compare the outcomes of patients undergoing open, video-assisted or robotic-assisted lobectomy by a highvolume surgeon. Results showed mortality, hospital length of stay and complications after robotic surgery were far less frequent compared to open lobectomy. In addition, the researchers found a significant drop in mortality among robotic lobectomy patients compared to video-assisted lobectomy patients.
At the University of Chicago Medicine, all of the thoracic surgeons are skilled robotic surgeons with extensive experience in lung cancer removal, providing Dr Mark Ferguson, MD, performs surgery Dr Mark Ferguson, MD, performs surgery at the University of Chicago Medicine added benefits for patient recovery. The leading-edge technology at the University of Chicago Medicine not only serves as a platform to perform robotic lung cancer surgery, but to develop and refine these surgical techniques for more and more indications in thoracic surgery, not just lobectomies and resections.
• For more information, please visit: www.uchospitals.edu/specialties/cancer/lung/to state-of-the-art treatment at the University of Chicago
Date of upload: 15th 2016
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