Tuesday, October 22, 2013

Rapid method to detect BRAF mutations in cancer tissue samples

Rapid method to detect BRAF mutations in cancer tissue samples


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22-Oct-2013



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Contact: Lauren Riley
lauren.riley@aacr.org
215-446-7155
American Association for Cancer Research






BOSTON A new diagnostic platform to detect BRAF mutations in melanoma and other cancer types is faster and more accurate compared with the standard method currently used in clinics, and this could help accelerate diagnosis and treatment, according to results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19-23.


About 50 percent of melanomas, and less frequently other cancer types, harbor mutations in the BRAF oncogene. To date, more than 30 different cancer-associated BRAF mutations have been identified. The most common are the BRAF V600 mutations.


The new molecular diagnostics (MDx) prototype platform developed by Biocartis in Mechelen, Belgium, can detect BRAF V600 mutations in about 90 minutes, requires no sample preparation, and is 95 percent in agreement with the standard method approved by clinical laboratory improvement amendments (CLIA).


"When you do molecular testing for BRAF mutations the way it is done in the clinic, it often takes three to four weeks to get the results back. A lot of that time is spent preparing the sample, including laser microdissection to isolate DNA from the tumor cells," said Filip Janku, M.D., Ph.D., an oncologist at MD Anderson Cancer Center in Houston, Texas. "With the MDx platform, it takes about two minutes to add fresh, frozen, or paraffin-embedded tumor samples to the sample cartridge and less than 90 minutes to get the results. This platform is capable of giving you an answer in an absolutely unprecedented time frame.


"We used MDx to detect BRAF mutations as a proof of principle. This new platform will be capable of detecting a variety of mutations, including KRAS, EGFR, and others for which there are FDA-approved targeted therapies," he added. "Unfortunately, we are still not in a position to offer targeted therapies to patients as soon as they come to the clinic, because it takes time to do molecular testing. Identifying the right treatment for patients early is crucial in cancer care. We need to invest more in developing assays and diagnostic platforms."


Janku and colleagues used 79 archival tumor samples to test the MDx platform. BRAF mutation status obtained using the CLIA-approved method was available for all these samples. The results generated using the MDx platform and CLIA-approved method were in agreement for 75 of the 79 samples. Of the four samples with discrepancies, the MDx platform but not the CLIA-approved method detected a BRAF V600E mutation in a colon cancer sample, and the MDx platform did not detect BRAF mutations in the remaining three samples that were reported to be BRAF-mutation positive by the CLIA-approved method.


Of interest, two of the three patients whose tumor samples tested positive for BRAF mutations by the CLIA-approved method but not the MDx platform were treated with BRAF/MEK inhibitors based on the CLIA results, and they did not respond to treatment.


###

This study was funded by Biocartis. Janku has no conflicts of interest to declare.


The 2013 International Conference on Molecular Targets and Cancer Therapeutics is being co-hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC).


This research will be presented at a press conference entitled "Guiding Treatment for BRAF- and BRCA-related Cancers" during the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on Monday, Oct. 22 at 9 a.m. ET in room 202 of the Hynes Convention Center in Boston, Mass. Reporters who cannot attend in person may call in using the following numbers:


  • U.S./Canada (toll-free): 800-446-2782
  • International (toll): 847-413-3235

To interview Filip Janku, contact Scott Merville at smerville@mdanderson.org or 713-792-0661. For other inquiries, contact Jeremy Moore at jeremy.moore@aacr.org or 215-446-7109.


About the American Association for Cancer Research

Founded in 1907, the American Association for Cancer Research (AACR) is the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.AACR.org. Follow the AACR on Twitter: @AACR. Follow the AACR on Facebook: http://www.facebook.com/aacr.org.


About the National Cancer Institute

The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).


About the European Organisation for Research and Treatment of Cancer

The European Organisation for the Research and Treatment of Cancer (EORTC) brings together European cancer clinical research experts from all disciplines for trans-national collaboration. Both multinational and multidisciplinary, the EORTC Network comprises more than 2,500 collaborators from all disciplines involved in cancer treatment and research in more than 300 hospitals in over 30 countries. Through translational and clinical research, the EORTC offers an integrated approach to drug development, drug evaluation programs and medical practices.

EORTC Headquarters, a unique pan European clinical research infrastructure, is based in Brussels, Belgium, from where its various activities are coordinated and run. http://www.eortc.org


Abstract Number: C198

Presenter: Filip Janku, M.D., Ph.D.


Title: BRAF mutation testing of archival tumor samples with a novel, rapid, fully-automated molecular diagnostics prototype platform


Authors: Helen J. Huang1, Bart Claes2, Gerald S. Falchook1, Benoit Devogelaere2, Aung Naing1, Siqing Fu1, Sarina Piha-Paul1, David S. Hong1, Veronica R. Holley1, Apostolia M. Tsimberidou1, Vanda M. Stepanek1, Kevin B. Kim1, Laura S. Angelo3, Vivek Subbiah1, Jennifer J. Wheler1, Ralph G. Zinner1, Daniel D. Karp1, Rajyalakshmi Luthra1, Erwin Sablon2, Geert Maertens2, Funda Meric-Bernstam1, Razelle Kurzrock4, Stefan Scherer2, Filip Janku1. 1UT MD Anderson Cancer Ctr., Houston, TX; 2Biocartis NV, Mechelen, Belgium; 3Baylor College of Medicine, Houston, TX; 4UCSD Moores Cancer Center, La Jolla, CA


Background: Novel, fast, and accurate diagnostic systems are needed for further implementation of personalized therapy. Mutations in the BRAF gene can provide actionable targets for cancer therapy in melanoma and other tumor types.


Methods: The molecular diagnostics (MDx) prototype platform (Biocartis, Mechelen, Belgium) is a fully integrated real-time PCR-based system with high sensitivity (1%) and quick turnaround time (

Results: Seventy-nine pts (melanoma, n=34; colorectal, n=20; papillary thyroid, n=6; ovarian, n=4; other cancers, n=15) with available tissue and CLIA laboratory BRAF results were identified (BRAF V600 mutation, n=49; wild-type BRAF, n=30). Of the 70 pts for whom the same tissue block was used for MDx and CLIA, BRAF results (V600 mutation yes/no) were concordant in 67 of them (96%; kappa 0.91; 95% CI 0.81-1.01; discrepancies: V600E mutation from CLIA only in prostate cancer, V600E mutation from CLIA only in melanoma, V600E mutation from MDx only in colon cancer). In addition, BRAF results by MDx were discrepant with CLIA in one case (melanoma) in the mutation subtype (V600K vs. V600E). In all 79 pts (including 9 patients with different blocks tested) MDx and CLIA BRAF results (V600 mutation yes/no) were concordant in 75 (95%; kappa 0.89; 95% CI 0.79-1.00) of them (additional discrepancy: V600K mutation from CLIA only in colon cancer). Of 49 pts with BRAF mutations detected by MDx, 30 were treated on protocols (on the basis of the CLIA lab results) with BRAF/MEK inhibitors and 8 (27%) had a partial response. Of interest, 2 of 3 pts with BRAF mutations from CLIA, but not MDx, received a BRAF/MEK inhibitor and did not respond. Detailed patient characteristics, mutation types and discrepancy analysis will be presented.


Conclusions: The BRAF V600 mutation MDx prototype platform is a fast (turn-around time about 1.5 hours) and simple (


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Rapid method to detect BRAF mutations in cancer tissue samples


[ Back to EurekAlert! ]

PUBLIC RELEASE DATE:

22-Oct-2013



[


| E-mail

]


Share Share

Contact: Lauren Riley
lauren.riley@aacr.org
215-446-7155
American Association for Cancer Research






BOSTON A new diagnostic platform to detect BRAF mutations in melanoma and other cancer types is faster and more accurate compared with the standard method currently used in clinics, and this could help accelerate diagnosis and treatment, according to results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19-23.


About 50 percent of melanomas, and less frequently other cancer types, harbor mutations in the BRAF oncogene. To date, more than 30 different cancer-associated BRAF mutations have been identified. The most common are the BRAF V600 mutations.


The new molecular diagnostics (MDx) prototype platform developed by Biocartis in Mechelen, Belgium, can detect BRAF V600 mutations in about 90 minutes, requires no sample preparation, and is 95 percent in agreement with the standard method approved by clinical laboratory improvement amendments (CLIA).


"When you do molecular testing for BRAF mutations the way it is done in the clinic, it often takes three to four weeks to get the results back. A lot of that time is spent preparing the sample, including laser microdissection to isolate DNA from the tumor cells," said Filip Janku, M.D., Ph.D., an oncologist at MD Anderson Cancer Center in Houston, Texas. "With the MDx platform, it takes about two minutes to add fresh, frozen, or paraffin-embedded tumor samples to the sample cartridge and less than 90 minutes to get the results. This platform is capable of giving you an answer in an absolutely unprecedented time frame.


"We used MDx to detect BRAF mutations as a proof of principle. This new platform will be capable of detecting a variety of mutations, including KRAS, EGFR, and others for which there are FDA-approved targeted therapies," he added. "Unfortunately, we are still not in a position to offer targeted therapies to patients as soon as they come to the clinic, because it takes time to do molecular testing. Identifying the right treatment for patients early is crucial in cancer care. We need to invest more in developing assays and diagnostic platforms."


Janku and colleagues used 79 archival tumor samples to test the MDx platform. BRAF mutation status obtained using the CLIA-approved method was available for all these samples. The results generated using the MDx platform and CLIA-approved method were in agreement for 75 of the 79 samples. Of the four samples with discrepancies, the MDx platform but not the CLIA-approved method detected a BRAF V600E mutation in a colon cancer sample, and the MDx platform did not detect BRAF mutations in the remaining three samples that were reported to be BRAF-mutation positive by the CLIA-approved method.


Of interest, two of the three patients whose tumor samples tested positive for BRAF mutations by the CLIA-approved method but not the MDx platform were treated with BRAF/MEK inhibitors based on the CLIA results, and they did not respond to treatment.


###

This study was funded by Biocartis. Janku has no conflicts of interest to declare.


The 2013 International Conference on Molecular Targets and Cancer Therapeutics is being co-hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC).


This research will be presented at a press conference entitled "Guiding Treatment for BRAF- and BRCA-related Cancers" during the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on Monday, Oct. 22 at 9 a.m. ET in room 202 of the Hynes Convention Center in Boston, Mass. Reporters who cannot attend in person may call in using the following numbers:


  • U.S./Canada (toll-free): 800-446-2782
  • International (toll): 847-413-3235

To interview Filip Janku, contact Scott Merville at smerville@mdanderson.org or 713-792-0661. For other inquiries, contact Jeremy Moore at jeremy.moore@aacr.org or 215-446-7109.


About the American Association for Cancer Research

Founded in 1907, the American Association for Cancer Research (AACR) is the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.AACR.org. Follow the AACR on Twitter: @AACR. Follow the AACR on Facebook: http://www.facebook.com/aacr.org.


About the National Cancer Institute

The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).


About the European Organisation for Research and Treatment of Cancer

The European Organisation for the Research and Treatment of Cancer (EORTC) brings together European cancer clinical research experts from all disciplines for trans-national collaboration. Both multinational and multidisciplinary, the EORTC Network comprises more than 2,500 collaborators from all disciplines involved in cancer treatment and research in more than 300 hospitals in over 30 countries. Through translational and clinical research, the EORTC offers an integrated approach to drug development, drug evaluation programs and medical practices.

EORTC Headquarters, a unique pan European clinical research infrastructure, is based in Brussels, Belgium, from where its various activities are coordinated and run. http://www.eortc.org


Abstract Number: C198

Presenter: Filip Janku, M.D., Ph.D.


Title: BRAF mutation testing of archival tumor samples with a novel, rapid, fully-automated molecular diagnostics prototype platform


Authors: Helen J. Huang1, Bart Claes2, Gerald S. Falchook1, Benoit Devogelaere2, Aung Naing1, Siqing Fu1, Sarina Piha-Paul1, David S. Hong1, Veronica R. Holley1, Apostolia M. Tsimberidou1, Vanda M. Stepanek1, Kevin B. Kim1, Laura S. Angelo3, Vivek Subbiah1, Jennifer J. Wheler1, Ralph G. Zinner1, Daniel D. Karp1, Rajyalakshmi Luthra1, Erwin Sablon2, Geert Maertens2, Funda Meric-Bernstam1, Razelle Kurzrock4, Stefan Scherer2, Filip Janku1. 1UT MD Anderson Cancer Ctr., Houston, TX; 2Biocartis NV, Mechelen, Belgium; 3Baylor College of Medicine, Houston, TX; 4UCSD Moores Cancer Center, La Jolla, CA


Background: Novel, fast, and accurate diagnostic systems are needed for further implementation of personalized therapy. Mutations in the BRAF gene can provide actionable targets for cancer therapy in melanoma and other tumor types.


Methods: The molecular diagnostics (MDx) prototype platform (Biocartis, Mechelen, Belgium) is a fully integrated real-time PCR-based system with high sensitivity (1%) and quick turnaround time (

Results: Seventy-nine pts (melanoma, n=34; colorectal, n=20; papillary thyroid, n=6; ovarian, n=4; other cancers, n=15) with available tissue and CLIA laboratory BRAF results were identified (BRAF V600 mutation, n=49; wild-type BRAF, n=30). Of the 70 pts for whom the same tissue block was used for MDx and CLIA, BRAF results (V600 mutation yes/no) were concordant in 67 of them (96%; kappa 0.91; 95% CI 0.81-1.01; discrepancies: V600E mutation from CLIA only in prostate cancer, V600E mutation from CLIA only in melanoma, V600E mutation from MDx only in colon cancer). In addition, BRAF results by MDx were discrepant with CLIA in one case (melanoma) in the mutation subtype (V600K vs. V600E). In all 79 pts (including 9 patients with different blocks tested) MDx and CLIA BRAF results (V600 mutation yes/no) were concordant in 75 (95%; kappa 0.89; 95% CI 0.79-1.00) of them (additional discrepancy: V600K mutation from CLIA only in colon cancer). Of 49 pts with BRAF mutations detected by MDx, 30 were treated on protocols (on the basis of the CLIA lab results) with BRAF/MEK inhibitors and 8 (27%) had a partial response. Of interest, 2 of 3 pts with BRAF mutations from CLIA, but not MDx, received a BRAF/MEK inhibitor and did not respond. Detailed patient characteristics, mutation types and discrepancy analysis will be presented.


Conclusions: The BRAF V600 mutation MDx prototype platform is a fast (turn-around time about 1.5 hours) and simple (


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]

 


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.




Source: http://www.eurekalert.org/pub_releases/2013-10/aafc-rmt101513.php
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