From Vanderbilt: “Project reveals importance of cancer gene mutation testing”

Vanderbilt U Bloc

Vanderbilt University

Jun. 8, 2017
Dagny Stuart
Dagny.stuart@vanderbilt.edu

An international genomic data-sharing consortium has analyzed nearly 19,000 patient genomic records and found that testing of patient tumors for relevant gene mutations often provides a roadmap for the use of effective therapies.

The American Association for Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE) is a multi-phase, multi-year data-sharing project launched in 2015 with eight academic centers. Vanderbilt-Ingram Cancer Center (VICC) is one of the institutions that shared de-identified genomic records from patients treated at the center to determine if genome sequencing can identify clinically useful mutations.

Mia Levy, M.D., Ph.D., Ingram Professor of Cancer Research and director of Cancer Health Informatics and Strategy, and Christine Micheel, Ph.D., research assistant professor of Medicine and managing editor of My Cancer Genome, led the VICC effort. Thomas Stricker, M.D., Ph.D., Michele LeNoue-Newton, Ph.D., and Lucy Wang also served as authors.

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Mia Levy, M.D., Ph.D.

One of the criticisms of molecular profiling is the time and financial cost involved in testing all patients since relatively small percentages of patients actually have a mutation that can be treated with a specific therapy. To determine the frequency of important mutations, the AACR Project GENIE group mapped all mutations to variant interpretations merged from other knowledge bases, including My Cancer Genome, OncoKB and Personalized Cancer Therapy.

The new analysis found that more than 30 percent of the patient samples had mutations that are clinically actionable, meaning patients potentially could be treated with targeted therapies already approved by the U.S. Food and Drug Administration (FDA) or which are being tested in clinical trials.

These frequencies varied widely across disease, from highly recurrent and druggable mutations in gastrointestinal stromal tumors (GIST) — 66 percent, almost all of which were mutations of KIT and PDGFRA associated with standard-of-care therapies — to tumor types with few actionable alterations, such as renal cell, prostate or pancreatic cancer.

Breast cancer is the disease with the highest fraction of patients who might benefit from existing investigational targeted therapies, due to frequent mutations of AKT1, ERBB2 and PIK3CA, account­ing for 38 percent of patients.

The investigators anticipate one of the benefits of GENIE will be an increased power for determining the clinical significance of mutations, particularly new indica­tions for approved drugs, as well as data-driven selection of tumors likely to contain actionable mutations for clinical trials.

The study was supported by funds from the AACR, Genentech, Boehringer Ingelheim, Pfizer, Eli Lilly, the Howard Hughes Medical Institute, the National Institutes of Health, the National Cancer Institute, the Princess Margaret Cancer Foundation, the Ontario Ministry of Health, Susan G. Komen, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the T.J. Martell Foundation, the Commonwealth Foundation, the Cancer Prevention and Research Institute of Texas, the Dutch Ministry of Health, and the Dutch Cancer Society.

The other seven institutions that participated in AACR Project GENIE phase 1 are: Dana-Farber Cancer Institute, Boston; Gustave Roussy Cancer Campus, Paris-Villejuif, France; The Netherlands Cancer Institute, Amsterdam, on behalf of the Center for Personalized Cancer Treatment, Utrecht, The Netherlands; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore; Memorial Sloan Kettering Cancer Center, New York; Princess Margaret Cancer Centre, Toronto; and University of Texas MD Anderson Cancer Center, Houston.

See the full article here .

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Commodore Cornelius Vanderbilt was in his 79th year when he decided to make the gift that founded Vanderbilt University in the spring of 1873.

The $1 million that he gave to endow and build the university was the commodore’s only major philanthropy. Methodist Bishop Holland N. McTyeire of Nashville, husband of Amelia Townsend who was a cousin of the commodore’s young second wife Frank Crawford, went to New York for medical treatment early in 1873 and spent time recovering in the Vanderbilt mansion. He won the commodore’s admiration and support for the project of building a university in the South that would “contribute to strengthening the ties which should exist between all sections of our common country.”

McTyeire chose the site for the campus, supervised the construction of buildings and personally planted many of the trees that today make Vanderbilt a national arboretum. At the outset, the university consisted of one Main Building (now Kirkland Hall), an astronomical observatory and houses for professors. Landon C. Garland was Vanderbilt’s first chancellor, serving from 1875 to 1893. He advised McTyeire in selecting the faculty, arranged the curriculum and set the policies of the university.

For the first 40 years of its existence, Vanderbilt was under the auspices of the Methodist Episcopal Church, South. The Vanderbilt Board of Trust severed its ties with the church in June 1914 as a result of a dispute with the bishops over who would appoint university trustees.

kirkland hallFrom the outset, Vanderbilt met two definitions of a university: It offered work in the liberal arts and sciences beyond the baccalaureate degree and it embraced several professional schools in addition to its college. James H. Kirkland, the longest serving chancellor in university history (1893-1937), followed Chancellor Garland. He guided Vanderbilt to rebuild after a fire in 1905 that consumed the main building, which was renamed in Kirkland’s honor, and all its contents. He also navigated the university through the separation from the Methodist Church. Notable advances in graduate studies were made under the third chancellor, Oliver Cromwell Carmichael (1937-46). He also created the Joint University Library, brought about by a coalition of Vanderbilt, Peabody College and Scarritt College.

Remarkable continuity has characterized the government of Vanderbilt. The original charter, issued in 1872, was amended in 1873 to make the legal name of the corporation “The Vanderbilt University.” The charter has not been altered since.

The university is self-governing under a Board of Trust that, since the beginning, has elected its own members and officers. The university’s general government is vested in the Board of Trust. The immediate government of the university is committed to the chancellor, who is elected by the Board of Trust.

The original Vanderbilt campus consisted of 75 acres. By 1960, the campus had spread to about 260 acres of land. When George Peabody College for Teachers merged with Vanderbilt in 1979, about 53 acres were added.

wyatt centerVanderbilt’s student enrollment tended to double itself each 25 years during the first century of the university’s history: 307 in the fall of 1875; 754 in 1900; 1,377 in 1925; 3,529 in 1950; 7,034 in 1975. In the fall of 1999 the enrollment was 10,127.

In the planning of Vanderbilt, the assumption seemed to be that it would be an all-male institution. Yet the board never enacted rules prohibiting women. At least one woman attended Vanderbilt classes every year from 1875 on. Most came to classes by courtesy of professors or as special or irregular (non-degree) students. From 1892 to 1901 women at Vanderbilt gained full legal equality except in one respect — access to dorms. In 1894 the faculty and board allowed women to compete for academic prizes. By 1897, four or five women entered with each freshman class. By 1913 the student body contained 78 women, or just more than 20 percent of the academic enrollment.

National recognition of the university’s status came in 1949 with election of Vanderbilt to membership in the select Association of American Universities. In the 1950s Vanderbilt began to outgrow its provincial roots and to measure its achievements by national standards under the leadership of Chancellor Harvie Branscomb. By its 90th anniversary in 1963, Vanderbilt for the first time ranked in the top 20 private universities in the United States.

Vanderbilt continued to excel in research, and the number of university buildings more than doubled under the leadership of Chancellors Alexander Heard (1963-1982) and Joe B. Wyatt (1982-2000), only the fifth and sixth chancellors in Vanderbilt’s long and distinguished history. Heard added three schools (Blair, the Owen Graduate School of Management and Peabody College) to the seven already existing and constructed three dozen buildings. During Wyatt’s tenure, Vanderbilt acquired or built one-third of the campus buildings and made great strides in diversity, volunteerism and technology.

The university grew and changed significantly under its seventh chancellor, Gordon Gee, who served from 2000 to 2007. Vanderbilt led the country in the rate of growth for academic research funding, which increased to more than $450 million and became one of the most selective undergraduate institutions in the country.

On March 1, 2008, Nicholas S. Zeppos was named Vanderbilt’s eighth chancellor after serving as interim chancellor beginning Aug. 1, 2007. Prior to that, he spent 2002-2008 as Vanderbilt’s provost, overseeing undergraduate, graduate and professional education programs as well as development, alumni relations and research efforts in liberal arts and sciences, engineering, music, education, business, law and divinity. He first came to Vanderbilt in 1987 as an assistant professor in the law school. In his first five years, Zeppos led the university through the most challenging economic times since the Great Depression, while continuing to attract the best students and faculty from across the country and around the world. Vanderbilt got through the economic crisis notably less scathed than many of its peers and began and remained committed to its much-praised enhanced financial aid policy for all undergraduates during the same timespan. The Martha Rivers Ingram Commons for first-year students opened in 2008 and College Halls, the next phase in the residential education system at Vanderbilt, is on track to open in the fall of 2014. During Zeppos’ first five years, Vanderbilt has drawn robust support from federal funding agencies, and the Medical Center entered into agreements with regional hospitals and health care systems in middle and east Tennessee that will bring Vanderbilt care to patients across the state.

studentsToday, Vanderbilt University is a private research university of about 6,500 undergraduates and 5,300 graduate and professional students. The university comprises 10 schools, a public policy center and The Freedom Forum First Amendment Center. Vanderbilt offers undergraduate programs in the liberal arts and sciences, engineering, music, education and human development as well as a full range of graduate and professional degrees. The university is consistently ranked as one of the nation’s top 20 universities by publications such as U.S. News & World Report, with several programs and disciplines ranking in the top 10.

Cutting-edge research and liberal arts, combined with strong ties to a distinguished medical center, creates an invigorating atmosphere where students tailor their education to meet their goals and researchers collaborate to solve complex questions affecting our health, culture and society.

Vanderbilt, an independent, privately supported university, and the separate, non-profit Vanderbilt University Medical Center share a respected name and enjoy close collaboration through education and research. Together, the number of people employed by these two organizations exceeds that of the largest private employer in the Middle Tennessee region.
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