Janet Rowley awarded Gruber Genetics Prize for chromosome studies

Discoveries established cancer as a genetic disease

July 1, 2009

Janet Rowley, MD

Janet Davison Rowley, MD, a founder in the field of cancer cytogenetics and a leader in molecular oncology, will receive the 2009 Genetics Prize of The Peter and Patricia Gruber Foundation for her research on recurrent chromosomal abnormalities in leukemias and lymphomas--discoveries that have revolutionized how cancer is understood and treated.

A 1998 recipient of the Lasker Award and the National Medal of Science, Rowley, 84, the Blum-Riese Distinguished Service Professor at the University of Chicago, is also being honored, according to the Gruber Foundation, for her "critical national and international leadership in the biomedical research community."

The Prize comes with a gold medal and an unrestricted cash prize of $500,000. It will be presented in Honolulu, Hawaii, on October 23 at the 59th Annual Meeting of the American Society of Human Genetics.

"Janet Rowley's work established that cancer is a genetic disease," says Mary-Claire King, a geneticist at the University of Washington. "She demonstrated that mutations in critical genes lead to specific forms of leukemia and lymphoma, and that one can determine the form of cancer present in a patient directly from the cancer's genes. We are still working from her paradigm."

Before Rowley, few scientists suspected that chromosomal aberrations caused tumors. The established view at the time was that abnormal chromosomes were manifestations of generalized chaos within leukemia and lymphoma cells. But Rowley believed something else was going on with those damaged pieces of DNA, and diligently pursued their study.

"I became a kind of missionary, saying that chromosome abnormalities were important and hematologists should know about them," Rowley recalls of those early--and often lonely--years in the field. "I got sort of amused tolerance at the beginning."

In the end, Rowley proved to be astonishingly prescient. Over the next decade, she made a number of remarkable discoveries, including the landmark finding that an abnormally short chromosome associated with chronic myelogenous leukemia (CML) was not a chromosome deletion, as many scientists had thought, but an exchange (translocation) of segments between two chromosomes.

Prior to this discovery, Rowley had an unusual career path. In 1940, she enrolled as an undergraduate at University of Chicago, at the age of 15. In 1945, she was one of only seven women out of 65 students entering the University of Chicago School of Medicine. In 1948, the day after graduating from medical school, she married fellow student, Donald Rowley. They had four children, all boys. She stayed home to raise them while working part-time with mentally disabled children.

Her scientific career got rolling only in 1962. On sabbatical with her husband in Oxford, she learned newly developed techniques of chromosome analysis. Back in Chicago, at the request of her clinical colleagues, she used these techniques to study the chromosomes of patients with leukemia. For the next decade she labored over the microscope, searching amid the seeming genetic chaos of leukemic cells for consistent chromosome abnormalities.

The first such abnormality had just been reported by Peter Nowell and colleague David Hungerford. They found that patients with chronic myelogenous leukemia had an abnormally small chromosome 22 in their tumor cells, which they labeled the "Philadelphia" chromosome.

The next step came in the early 1970's when geneticists perfected the art of chromosome "banding," a way of visualizing segments of chromosomes with more precision. Again, Rowley learned these techniques during a sabbatical in Oxford. They enabled her to discover that chromosomes from leukemic cells not only lost genetic material, they sometimes exchanged it. Early in 1972, Rowley discovered the first such "translocation," an exchange of small pieces of DNA between chromosomes 8 and 21 in patients with acute myeloblastic leukemia.

Later that same year, she found that the "Philadelphia" chromosome was also the result of a translocation. In patients with CML, a crucial segment of chromosome 22 broke off and moved to chromosome 9, where it did not belong. At the same time, a tiny piece of chromosome 9, which included an important cancer-causing gene, had moved to the breakpoint on chromosome 22. Because of this transfer from one chromosome to another, important genes that regulated cell growth and division were no longer located in their normal position on the chromosome. This provided critical evidence that cancer was a genetic disorder.

Rowley and her colleagues subsequently identified several other chromosome translocations that were characteristic of specific malignancies, such as the 14;18 translocation seen in follicular lymphoma, and the 15;17 translocation that causes acute promyelocytic leukemia (APL).

Quickly picking up on her lead that specific translocations defined specific forms of cancer, scientists around the world joined the search for chromosomes that either exchanged genetic material or in some cases lost it altogether in a process known as a "deletion." Others used the translocations as road maps to narrow the search for specific genes that were disrupted by chromosome damage, thus opening up the current era of cancer genetics.

Rowley's contributions to identifying chromosomal abnormalities in leukemias and lymphomas have changed the way these diseases are diagnosed and treated. Today, newer techniques can identify the DNA damage within individual cells, offering a much more precise diagnosis of disease--and more effective treatments.

The research paid other benefits. The development of the drug imatinib (Gleevec)--one of the most successful targeted cancer therapies to date--stems directly from Rowley's work on the 9;22 translocation. Imatinib blocks the abnormal protein produced by that translocation.

Rowley's research continues at her lab at the University of Chicago, where she has inspired and generously mentored countless students and postgraduate fellows during the ensuing years. Cancer cytogenetics continues to fascinate--and challenge--her.

"We're still working on the leukemias," she says. "There's a lot of evidence that translocations and other chromosome abnormalities aren't sufficient to make a cell malignant. We're looking for the other mechanisms involved."

"As Chair of this year's Selection Committee for the Gruber Prize in Genetics, I am delighted that the Committee recognized such a distinguished scientist and individual as Dr. Rowley," says Elizabeth Blackburn, the Morris Herzstein Professor of Biology and Physiology in the Department of Biochemistry and Biophysics at the University of California, San Francisco. "Her major contributions to the understanding of the underpinnings of cancer make her an outstanding choice for this important Prize and truly reflect the goal of this Prize in celebrating the field of Genetics."

The Gruber International Prize Program honors contemporary individuals in the fields of Cosmology, Genetics, Neuroscience, Justice and Women's Rights, whose groundbreaking work provides new models that inspire and enable fundamental shifts in knowledge and culture. The Selection Advisory Boards choose individuals whose contributions in their respective fields advance our knowledge, potentially have a profound impact on our lives, and, in the case of the Justice and Women's Rights Prizes, demonstrate courage and commitment in the face of significant obstacles.

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