BRAF Mutation Varies in Thyroid Cancer

RAF Mutation Varies in Thyroid Cancer

Published: Aug 26, 2013

By  Nancy Walsh , Staff Writer, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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Action Points

• BRAF mutation was found to be an independent predictor of central lymph node metastases in the overall cohort of patients with papillary thyroid cancer, including those with aggressive or follicular subtypes.
• Note, however, that this relationship lost significance when only classical variant papillary thyroid cancer was included in the analysis.

Whether BRAF mutations can be used to determine the likelihood of lymph node metastases of papillary thyroid cancer remains unclear because of the mutation's strong association with aggressive subtypes of the cancer, researchers reported.

In a multivariate analysis of almost 400 patients with any thyroid cancer subtype who underwent total thyroidectomy and central lymph node dissection, independent associations with lymph node metastases were found for BRAF mutations (OR 2.37, 95% CI 1.41-3.98, P=0.001), tumor size greater than 2 cm (OR 1.62, 95% CI 1.01-2.61, P=0.045), and extra-thyroid extension (OR 2.77, 95% CI 1.58-4.86, P<0 .001="" a="" according="" href="http://www.hopkinsmedicine.org/profiles/results/directory/profile/0007252/martha-zeiger" style="color: #003f85; outline-style: none; text-decoration: none;" target="_blank" to="">Martha A. Zeiger, MD

, of Johns Hopkins School of Medicine, and colleagues.

However, when the analysis was limited to the most common classical variant, papillary thyroid cancer, and the highly aggressive subtypes that are closely associated with BRAFmutations such as the follicular variant were excluded, there was no significant association between the mutation and lymph node metastases (P=0.244), the researchers reported in theJournal of Clinical Endocrinology & Metabolism.

"Regarding [papillary thyroid cancer] as a homogeneous entity could lead to miscalculations and/or misunderstandings of relationships between independent predictors, such as BRAFstatus, and dependent outcomes, including [lymph node metastases]," Zeiger and colleagues wrote.

While papillary thyroid cancer usually carries a good prognosis, patients with lymph node involvement at the time of diagnosis are at increased risk for recurrence.

Whether or not all patients should undergo bilateral prophylactic lymph node dissection following thyroidectomy has been a subject of controversy, with advocates arguing that some studies have found occult nodal metastases in as many as 80% of patients, and opponents suggesting that most occult micrometastases aren't clinically important.

"Because of the controversy surrounding the appropriate surgical management of [papillary thyroid cancer], more accurate risk stratification is needed to guide treatment," the researchers stated.

They noted that "molecular tumor profiling" has become increasingly popular as a diagnostic and prognostic aid, with the BRAF V600E mutation that activates the MAPK pathway being a focus of considerable attention.

This mutation also has been linked with other types of cancer, such as leukemia, melanoma, and lung cancer.

But the evidence for BRAF mutations as being predictive in thyroid cancer has been conflicting, and studies have had limitations such as selection bias.

Therefore, to clarify the prognostic utility of BRAF mutations for lymph node metastases in thyroid cancer, Zeiger and colleagues conducted a retrospective study of all 388 patients who underwent thyroidectomy followed by central lymph node dissection in four tertiary care centers between January 2009 and December 2011.

A total of 315 of the patients had classical variant papillary thyroid cancer, 41 had the follicular variant, 31 had the tall cell variant, and one had a poorly differentiated tumor.

Among the classical variant group, more than three-quarters were women, and mean age was 46. The mean tumor size was 1.89 cm, and 80% had the BRAF V600E mutation.

The multivariate analysis limited to this group found significant positive associations for lymph node metastases with tumor size greater than 2 cm (OR 2.04, 95% CI 1.20-3.48,P=0.009) and extra-thyroid extension (OR 2.20, 95% CI 1.18-4.09, P=0.013), but not with theBRAF mutation.

Age of 45 and older had a significant negative association with lymph node metastases (OR 0.41, 95% CI 0.25-0.67, P<0 .001="" p="">

In the subgroup with the follicular variant subtype, strong independent associations with lymph node metastases were found for the BRAF mutation (OR 9.69, 95% CI 1.05-89.33,P=0.45) and extra-thyroid extension (OR 34.04, 95% CI 1.4-827.51, P=0.030).

In the other subgroup, which included the aggressive forms such as the tall cell variant, 71% of patients with the BRAF mutation had metastases to the lymph nodes, and none of the patients without the mutation had metastatic disease.

Bivariate analysis in this subgroup found that the BRAF mutation was the only independent predictor of lymph node metastases (P=0.006).

These findings suggest that "BRAF mutation may be differentially associated with the risk of [lymph node metastases] across [papillary thyroid cancer] subtypes," the researchers stated.

"Further research is warranted before factors such as BRAF mutation are included in treatment algorithms that do not take into account tumor histology," they cautioned.

This additional research should include prospective studies involving multiple centers, they added.

Limitations of the study included small numbers of patients with the aggressive subtypes and its retrospective design.

The study was supported by the Johns Hopkins University School of Medicine.

The authors reported no financial disclosures.

'via Blog this'

Bayer's Nexavar gets priority review as thyroid cancer drug - Yahoo! News

FRANKFURT (Reuters) - Bayer's cancer drug Nexavar was given priority review status by U.S. healthcare regulators for the oral drug's use against a difficult-to-treat type of thyroid cancer, the company said on Tuesday.

The U.S. Food and Drug Administration aims to complete the priority review within six months, rather than the standard review of about 10 months, Bayer said.

Bayer and development partner Onyx Pharmaceuticals are seeking a wider use for Nexavar to include treatment of patients with thyroid cancer that returned despite previous surgery and treatment with radioactive iodine, a group with a particularly poor prospect of survival.

Nexavar is already approved to treat liver as well as kidney cancer and it is also being tested on breast cancer patients.

(Reporting by Ludwig Burger)

'via Blog this'

Thyroid Cancer - Symptoms, Causes, Treatment, Exams and Tests for Thyroid Cancer

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What is thyroid cancer?

Thyroid cancer is a disease that you get when abnormal cells begin to grow in your thyroid gland . The thyroid gland is shaped like a butterfly and is located in the front of your neck. It makes hormones that regulate the way your body uses energy and that help your body work normally.

Thyroid cancer is an uncommon type of cancer. Most people who have it do very well, because the cancer is usually found early and the treatments work well. After it is treated, thyroid cancer may come back, sometimes many years after treatment.

What causes thyroid cancer?

Experts don't know what causes thyroid cancer. But like other cancers, changes in the DNA of your cells seem to play a role. These DNA changes may include changes that are inherited as well as those that happen as you get older.

People who have been exposed to a lot of radiation have a greater chance of getting thyroid cancer.

A dental X-ray now and then will not increase your chance of getting thyroid cancer. But past radiation treatment of your head, neck, or chest (especially during childhood) can put you at risk of getting thyroid cancer.

What are the symptoms?

Thyroid cancer can cause several symptoms:

• You may get a lump or swelling in your neck. This is the most common symptom.
• You may have pain in your neck and sometimes in your ears.
• You may have trouble swallowing.
• You may have trouble breathing or have constant wheezing.
• Your voice may be hoarse.
• You may have a frequent cough that is not related to a cold.

Some people may not have any symptoms. Their doctors may find a lump or nodulein the neck during a routine physical exam.

How is thyroid cancer diagnosed?

If you have a lump in your neck that could be thyroid cancer, your doctor may do abiopsy of your thyroid gland to check for cancer cells. A biopsy is a simple procedure in which a small piece of the thyroid tissue is removed, usually with a needle, and then checked.

Sometimes the results of a biopsy are not clear. In this case, you may need surgery to remove all or part of your thyroid gland before you find out if you have thyroid cancer.

How is it treated?

Thyroid cancer is treated with surgery and often with radioactive iodine. It rarely needs radiation therapy or chemotherapy. What treatment you need depends on your age, the type of thyroid cancer you have, and the stage of your disease. Stage refers to how severe the disease is and how far, if at all, the cancer has spread.

Your doctor may also remove lymph nodes in your neck to see if cancer has spread beyond the thyroid

Finding out that you have cancer can be overwhelming. It?s common to feel scared, sad, or even angry. Talking to others who have had thyroid cancer may help. Ask your doctor about cancer support groups in your area.

Can thyroid cancer be prevented?

Most thyroid cancer cannot be prevented.

One rare type of thyroid cancer, called medullary thyroid cancer (MTC), runs in families. A genetic test can tell you if you have a greater chance of getting MTC. If this test shows that you have an increased risk, you can have your thyroid gland removed to prevent thyroid cancer later in life.

Frequently Asked Questions

Learning about thyroid cancer:	What is thyroid cancer? What causes thyroid cancer? What are the symptoms of thyroid cancer? What increases my risk for thyroid cancer? Can I prevent thyroid cancer? When do I need to see my doctor?
Being diagnosed:	How will my doctor diagnose thyroid cancer? What is a thyroid scan? What is a thyroid ultrasound? What types of blood tests will I need? Will I need a thyroid biopsy?
Getting treatment:	How is thyroid cancer treated? What type of medicines will I need to take? Will I need surgery? Will I have to have radiation therapy?
Living with thyroid cancer:	How can I cope with the side effects of treatment? What happens if thyroid cancer comes back?

Article: Experts Call for Redefinition of 'Cancer'

Many growths are slow to progress and nonlethal, only leading to unnecessary treatment, panel says

WebMD News from HealthDay

By E.J. Mundell

HealthDay Reporter

TUESDAY, July 30 (HealthDay News) -- A panel of experts commissioned by the U.S. National Cancer Institute says that the word "cancer" may need to be redefined to prevent overdiagnosis and overtreatment of conditions that are often not lethal.

Writing in the July 29 online edition of the Journal of the American Medical Association, the experts say that widespread cancer screening programs turn up too many growths that would not progress to a lethal stage and are considered "indolent."

Most patients do not understand that distinction, however, and "the word 'cancer' often invokes the specter of an inexorably lethal process," wrote Dr. Laura Esserman of the University of California, San Francisco, Dr. Ian Thompson Jr. of the University of Texas Health Science Center at San Antonio, and Dr. Brian Reid of the Fred Hutchinson Cancer Research Institute in Seattle.

Cancer can take "multiple pathways," the three say, "not all of which progress to metastases and death, and include indolent disease that causes no harm during the patient's lifetime."

This re-examination of what constitutes a cancer diagnosis has been spurred by the explosion over the past few decades of sophisticated screening measures such as the mammogram, colonoscopy and the PSA blood test (for prostate cancer). All were heralded as potentially lifesaving, and many predicted that widespread adoption of these tests would catch disease early and cause cancer rates to fall.

But the cancer screening story has turned out differently, the panel noted, because many of the lesions picked up on screening have turned out to be indolent.

"Screening for breast cancer and prostate cancer appears to detect more cancers that are potentially clinically insignificant," the experts said. The same might be said for screens for thyroid cancers and melanomas -- certainly, lives have been saved because tumors were detected and treated, but "the detection of indolent disease" has risen, too, the panelists wrote.

Issues like this have played out in recent years. The United States Preventive Services Task Force, an influential government panel, caused a furor in 2009 when it called for the abandonment of regular mammography screening for women under 50, reasoning that the benefits of screening for younger women were outweighed by the risks. The same panel also rejected the widespread use of the PSA test, noting that it too often picked up slow-growing lesions that might never harm men's health.

According to the experts writing in JAMA, the best-case scenario for cancer screening is when the tumor is slow-growing but also typically progressive. Colon cancer often acts in this way, the team noted, and colonoscopy has become an "effective" screening program.

In the meantime, however, "overdiagnosis" occurs. The experts say a redefinition of cancer may be needed to quell patient fears over indolent lesions and curb overdiagnosis and overtreatment.

"Use of the term 'cancer' should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated," they wrote. Other growths would be classified in a lesser category, "indolent lesions of epithelial origin" (IDLE).

A change in mindset may also be needed for patients and health care workers alike. "Physicians, patients and the general public must recognize that overdiagnosis is common and occurs more frequently with cancer screening," the team wrote.

The recommendations are sure to spur debate, but one outside expert said that debate may be what is needed on this issue.

"We're still having trouble convincing people that the things that get found as a consequence of mammography and PSA testing and other screening devices are not always malignancies in the classical sense that will kill you," Dr. Harold Varmus, director of the National Cancer Institute, told The New York Times. "Just as the general public is catching up to this idea, there are scientists who are catching up, too."

But not everyone agrees. Dr. Larry Norton is medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan-Kettering Cancer Center in New York City. He said the problem is that even some relatively indolent breast growths, such as ductal carcinoma in situ (DCIS), can go on to become progressive, lethal cancers.

"Which cases of DCIS will turn into an aggressive cancer and which ones won't?" he told the Times. "I wish we knew that. We don't have very accurate ways of looking at tissue and looking at tumors under the microscope and knowing with great certainty that it is a slow-growing cancer."

A Concise Guide for Sutent User Newbies (new users) | Cancer Survivors Network

Here's a good beginning guide to Sutent.  It's geard toward kidney cancer patients, but it's also good advice for those of us using Sutent for other cancers.

A Concise Guide for Sutent User Newbies (new users)

Eliezer2 Posts: 34  Joined: Aug 2012

Jan 24, 2013 - 1:13 pm A Concise Guide for Sutent User Newbies (new users) *  Sutent does not "work" for everyone, but it does work for a LOT of people.  No one knows for how long it can work because it has only been on the market for a few years. *  I have stage 4 RCC with a lot of small mets in my lungs.  I am one of the people for whom Sutent works and I recommend it!  I am not getting any kickbacks for saying so from the manufacturer (alas).  I have been on it for about 19 months. *  At this point the disease itself is not directly causing me any disruption, discomfort, or pain.  Any discomfort I have is not directly from the disease but from the side effects of the Sutent.  The price for halting the progression of the disease is those side effects.  These vary a lot across patients and even for individual patients across Sutent cycles.  The side effects are not trivial, but generally not so bad as to prevent normal functioning and quality of life (at least by my experience).  Coping with cancer at this point is simply coping with those side effects, but nothing worse than that. *  The side effects of Sutent vary from the mild to the very annoying.  They also vary from the medically irrelevant to the medically potentially dangerous. Side Effects: *  I find that they are milder on a two-week-on-one-week-off cycle than the 4-2 week version.  I am on the full monty, the 50 mg dose, which some people cannot tolerate.  I think you are better off on 50 mg with shorter cycles than 37.5 with longer cycles. *  I think the two common and most dangerous potentially for most people are high blood pressure and slow thyroid functions.  There are some people who experience disruption of liver functions or heart functions; one needs to keep an eye on those things.   Blood pressure and slow thyroid issues are relatively easy to treat and control but are dangerous if not controlled.  Simple blood pressure meds work for me and I go off them when I am on the breaks in the Sutent cycle.  Slow thyroid gets fixed with a thyroid supplement that has no other side effects.  My thryoid has gotten slower and slower and I have had to adjust the thyroid supplement accordingly, but nothing worse than that.  Slow thyroid and high blood pressure are actually a mixed BLESSING, because they are highly correlated with the Sutent being EFFECTIVE! *  Mildly annoying side effects:     -  MANY people get mouth, hand, feet sores.  I have gotten none, but I think my experience is not typical.  I understand these are manageable.    -  Taste changes in mouth late in cycle - spicy foods, salty, alcohol, mouth wash are very irritating when this happens.   Taste changes are milder on a 2-1 cycle compared with 4-2.    -  General muscle weakness in arms and legs late in the cycle, disappears during Sutent break.  These are also milder on 2-1 cycle compared with 4-2.  Just take stairs slower and carry fewer groceries.      -  I get watery eyes late in cycle.  Nothing to do about it.      -  My body temp drops quite low and I feel cold a lot.  Drops to 35 degrees C (94.8 F).  Might be thyroid related, or not.  Nothing to do but turn up the thermostat and add layers.     - General feelings of tiredness and fatigue.  Fixed by taking naps.      - Hemoglobin can drop.  Fix by taking iron supplement.  Blood fats (cholesterol and triglycerides) can shoot up, partly because of thyroid.  Adjust diet and, if necessary, take a pill that knocks them back down.   -  Hair turning white and skin pale.  I do not care much about this (on male geezers it is supposed tolook distinguished) but women patients complain a lot about it.  Can cure it with hair color.   My skin is a little dry, including in some unmentionable spots, but nothing some skin cream or Vaseline cannot fix. *  Very annoying side effects:    - For me, the only really serious annoyance has been gastro side effects:  the "runs," painful gas, cramps, sometimes nausea.  I have been wrestling with finding ways to control this for over a year and a half.  Most people seem to control it more easily than me, but what they use has not helped me.  This past month I have tried a couple of new things and at long last they seem to be working.  For me, this has been the major factor negatively impacting quality of life, but really the only such factor. *   Emotional side:  This of course also varies widely across people.  I was pretty scared and stressed in the first few weeks after I discovered I had mets in lungs and was Stage 4, rather than Stage 1.  After that, I made my peace with it and I would say that at this point I am not affected emotionally at all, am as chipper and optimistic as healthy people my age (I am 62).  I live a normal life, work, do pretty much all the things that healthy guys my age do, minus the jogging and weight lifting.  When I was first diagnosed, I was sent by the oncologists to a social worker for counseling.  She invited me into her office with boxes of tissues, since so many people sit and cry there under the circumstances.  I ended up telling her jokes and picking up HER spirits.  I am not depressed, I am no moodier than before I got cancer.  I do not feel dread on a day-to-day basis.  My most distressing experiences are all gastro side effects.   I am somewhat religiously observant but I do NOT think my emotional state has anything to do with that. *  I have LOTS of small mets in my lungs.  I can also do 30 pushups at age 62 (how many healthy blokes my age can say that?) and my pulmonary functioning levels are those of a health 45 year old (how many healthy blokes my age can say that?).  I do get out of breath more easily, but I attribute that to cutting back on exercise when I turned Stage 4. * I do still get a bit nervous when waiting for results from CT's and similar, and I have put my financial affairs in order, just in case.  But at age 62, EVERYONE should do THAT.  Once put in order, I ignore the subject altogether and get on with enjoying life.  *  Do things you like to do and that give you pleasure.  There is life after RCC!

Selumetinib-Enhanced Radioiodine Uptake in Advanced Thyroid Cancer — NEJM

Now this sounds interesting!  I hope the study is expanded.

ORIGINAL ARTICLE

Selumetinib-Enhanced Radioiodine Uptake in Advanced Thyroid Cancer

Alan L. Ho, M.D., Ph.D., Ravinder K. Grewal, M.D., Rebecca Leboeuf, M.D., Eric J. Sherman, M.D., David G. Pfister, M.D., Desiree Deandreis, M.D., Keith S. Pentlow, M.Sc., Pat B. Zanzonico, Ph.D., Sofia Haque, M.D., Somali Gavane, M.D., Ronald A. Ghossein, M.D., Julio C. Ricarte-Filho, Ph.D., José M. Domínguez, M.D., Ronglai Shen, Ph.D., R. Michael Tuttle, M.D., Steve M. Larson, M.D., and James A. Fagin, M.D.

N Engl J Med 2013; 368:623-632February 14, 2013DOI: 10.1056/NEJMoa1209288

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BACKGROUND

Metastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis. In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) pathway antagonists increase the expression of the sodium–iodide symporter and uptake of iodine. Their effects in humans are not known.

METHODS

We conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. After stimulation with thyrotropin alfa, dosimetry with iodine-124 positron-emission tomography (PET) was performed before and 4 weeks after treatment with selumetinib (75 mg twice daily). If the second iodine-124 PET study indicated that a dose of iodine-131 of 2000 cGy or more could be delivered to the metastatic lesion or lesions, therapeutic radioiodine was administered while the patient was receiving selumetinib.

RESULTS

Of 24 patients screened for the study, 20 could be evaluated. The median age was 61 years (range, 44 to 77), and 11 patients were men. Nine patients had tumors with BRAF mutations, and 5 patients had tumors with mutations of NRAS. Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients withBRAF mutations and 5 of 5 patients with NRAS mutations). Eight of these 12 patients reached the dosimetry threshold for radioiodine therapy, including all 5 patients with NRAS mutations. Of the 8 patients treated with radioiodine, 5 had confirmed partial responses and 3 had stable disease; all patients had decreases in serum thyroglobulin levels (mean reduction, 89%). No toxic effects of grade 3 or higher attributable by the investigators to selumetinib were observed. One patient received a diagnosis of myelodysplastic syndrome more than 51 weeks after radioiodine treatment, with progression to acute leukemia.

CONCLUSIONS

Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. (Funded by the American Thyroid Association and others; ClinicalTrials.gov number, NCT00970359.)

Supported by grants from the American Thyroid Association, the Society of Memorial Sloan-Kettering Cancer Center, the National Institutes of Health (RO1-CA50706 and RO1-CA72598), AstraZeneca, and Genzyme, as well as funding from the Lefkofsky Family, Margot Rosenberg Pulitzer, Byrne, and J. Randolph Hearst foundations. The iodine-124 PET studies were supported in part by a grant from the In-Vivo Cellular and Molecular Imaging Center (P50 086438-10). Dr. Domínguez was supported in part by a grant from Pontificia Universidad Católica de Chile and Becas Chile (76100021), and Dr. Deandreis by a grant from Fondation de France (2010-12521).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank the research study staff, particularly Susan Korte, Alex F. Mak, Brynna Lipson, Donna Lisa, and Lisa Cox, R.N.

SOURCE INFORMATION

From the Head and Neck Oncology Service (A.L.H., E.J.S., D.G.P.) and the Endocrinology Service (R.L., R.M.T., J.A.F.), Department of Medicine, and the Departments of Radiology (R.K.G., D.D., S.H., S.G., S.M.L.), Medical Physics (K.S.P., P.B.Z.), Pathology (R.A.G.), and Human Oncology and Pathogenesis (J.C.R.-F., J.M.D., J.A.F.), and the Epidemiology–Biostatistics (R.S.) and Molecular Pharmacology and Chemistry (S.M.L.) Programs, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York.

Address reprint requests to Dr. Fagin at the Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10065.

TROVAGENE :: TROVAGENE :: Revolutionary Molecular Diagnostics

Trovagene to Study Transrenal BRAF Mutations in Primary and Metastatic Cancers

1/3/2013

Study with MD Anderson will compare detection of BRAF mutations in urine to biopsy samples, and monitor therapeutic response, outcomes

 

SAN DIEGO, January 3, 2013 -- Trovagene, Inc. (NASDAQ: TROV), a developer of transrenal molecular diagnostics, announced that it has entered into a clinical collaboration with The University of Texas MD Anderson Cancer Center to detect transrenal BRAFmutations in the urine of patients with advanced or metastatic cancers.

Researchers will use Trovagene’s proprietary transrenal DNA (TrDNA) detection technology to evaluate BRAF mutation status in urine as compared to tissue biopsy. The study also calls for monitoring of mutation levels in the urine at planned intervals during and after treatment to assess outcomes including: response rate (RR); stable disease (SD); progression-free survival (PFS); and overall survival (OS). Results from patients who receive therapy that reflects their BRAF mutation status (e.g., BRAF inhibitors, MEK inhibitors) will be compared to outcomes for patients who receive standard-of-care therapy regardless of mutation status.

According to recent estimates, BRAF mutations are present in more than 20% of all cancers, and in 40% and 43% of all thyroid and skin cancer samples, respectively¹. Several targeted therapies for BRAF-mutated melanomas are already on the market and in development, including BRAF inhibitors vemurafenib (Zelboraf^®) and dabrafenib; and trametinib, a MEK inhibitor.

 “One of the  potential benefits of TrDNA would be its utility as a systemic, liquid biopsy, providing real-time information that may help guide targeted therapy decisions, and then help clinicians more easily monitor a patient’s therapeutic response and disease state,” said Filip Janku, MD, PhD, principal investigator for the study at MD Anderson. “A urine-based assay that reliably and cost-effectively detects mutations would be extremely useful as an aid in personalized medicine.”

"This study represents a first-of-its kind look at how urine-based mutation detection can be used to track patients from initial diagnosis through therapy, and then to monitor for early signs of progression,” said Dr. Charlie Rodi, chief technology officer at Trovagene. “We are pleased to sponsor this study with MD Anderson, and look forward to learning more about the unique properties and clinical utilities of our transrenal mutation assays.”

1.   Prevalence of BRAF mutations in various cancers. Sanger COSMIC site.http://cancer.sanger.ac.uk/cosmic/gene/overview?ln=BRAF


About Trovagene, Inc.
Headquartered in San Diego, California, Trovagene is developing its patented technology for the detection of transrenal DNA and RNA, short nucleic acid fragments, originating from normal and diseased cell death that cross the kidney barrier and can be detected in urine.  Trovagene is leveraging its intellectual property in oncogene mutations via out-licensing and use of its transrenal technologies to extend oncogene mutation detection using urine as a sample.  As a non-invasive and abundant sample, urine may overcome many of the cost and collection challenges associated with biopsy, as well as the volume limitations of blood.

Trovagene has a strong patent position as it relates to transrenal molecular testing. It has U.S. and European patent applications and issued patents that cover testing for HPV and other infectious diseases, cancer, transplantation, prenatal and genetic testing. In addition, it owns worldwide rights to nucleophosmin-1 (NPM1), an informative biomarker for acute myelogenous leukemia (AML) and mutations in the SF3B1 gene, which have been shown to be associated with chemotherapy response in chronic lymphocytic leukemia (CLL) patients, as well as other hematologic malignancies.

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as "anticipate," "believe," "forecast," "estimated" and "intend," among others. These forward-looking statements are based on Trovagene's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any medical diagnostic tests under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful or that any product will receive regulatory approval for any indication or prove to be commercially successful. Trovagene does not undertake an obligation to update or revise any forward-looking statement.  Investors should read the risk factors set forth in Trovagene's Form 10-K for the year ended December 31, 2011 and other periodic reports filed with the Securities and Exchange Commission.

Contacts
Trovagene, Inc.
Keith McCormick
VP, Commercial Operations
+1 (858) 952-7640
kmccormick@trovagene.com
http://www.trovagene.com