Borrowing from two disciplines, genomics and proteomics, the field of molecular diagnostics determines which genes and proteins interact in a cell, and focuses on identifying changes in patterns associated with different types of cancerous or precancerous cells. The identification of these patterns is improving clinicians’ ability to diagnose cancers and provide more precise prognosis and treatments.
Ken Kron fostered an interest in genetics and molecular biology five years ago at Mount Sinai, and is now completing his PhD studies in the lab of Lunenfeld scientist Dr. Bharati Bapat, whose research team bridges clinical pathology with molecular diagnostics.
“Cancer genetics held tremendous appeal for me as a researcher because of the opportunity to provide a positive outcome to patients and their families, in helping give valuable prognostic information through our work,” says Ken. “The potential of molecular testing to help patients is tangible, since this can help enable optimal screening methods before the disease occurs and provide decision-making assistance in selecting the best treatment.”
In the lab, Ken focuses on uncovering the causes of prostate cancer by taking a genetic and epigenetic approach, the latter examining changes in gene function that do not disrupt the underlying DNA sequence, but are instead a reversible change. DNA methylation, for example, is a normal process that can tune the activity state of a gene. The degree of DNA methylation of the control regions of a gene influences the level or intensity of that gene’s expression—thus impacting various cell functions.
Many cancer biologists agree that DNA methylation—the process in which enzymes add methyl groups onto genes and block their activity—and other so-called epigenetic changes may be as important as genetic mutations in causing cancer.
“Frequent, abnormal increases or decreases in DNA methylation are found in most human cancers and contribute to their development,” explains Ken. “Each tumour tends to have its own unique pattern, or signature, of DNA methylation. By studying changes in DNA methylation, we hope to extract knowledge that will contribute to more accurate and personalized diagnoses and therapies for prostate cancer.”
While various groups internationally are working to uncover key markers or epigenetic changes indicative of cancer, Dr. Bapat, Ken and others in the lab are one of the few groups in Canada exploring DNA methylation in both prostate and colorectal cancers. Other areas of epigenetic investigation may be focused on histone modifications, or non-coding regions such as micro RNAs—these types of changes and their impact on cancer induction and progression are an emerging area of study.
Ken is also engaged in an ongoing project in the Bapat lab that involves the use of an innovative profiling technique to screen the genomes of prostate cancer patients at various stages of progression. This process will reveal genetic markers to help pathologists, surgeons, oncologists and urologists better understand a patient’s prognosis, and ultimately determine optimal treatment on a case-by-case basis. “We work collaboratively with our colleagues in the hospital to bridge the gap between the lab and the clinic,” says Ken, noting that the newly discovered biomarkers will be used to develop new tests that may allow earlier detection and risk assessment of prostate cancer.
“We expect that fine-tuning the diagnostic measures for prostate cancer will help reduce the amount of unnecessary biopsies by providing greater accuracy than pre-operative Prostate-Specific Antigen (PSA) tests,” says Ken.
Another aspect of Ken’s recent work focuses on the development of non-invasive diagnostic tests for prostate cancer. He and other members of the lab have shown that changes in DNA methylation tied to prostate cancer can be detected in a urine sample. If shown to be reliable, this methodology could not only replace the need for invasive tumour biopsies, but also allow preventative medicine and monitoring of treatment effectiveness over time. Dr. Bapat’s lab is already testing urine and blood samples to detect epigenetic signatures that will avoid (or minimize) some surgical procedures in the future.
“The development of more non-invasive tests such as the technique we are developing has the potential to transform the way patients receive care and the way physicians make diagnoses,” says Dr. Bapat. “In addition to facilitating the development of such applications, Ken’s work is shedding light on the underlying biological pathways and their significance in tumour progression and disease outcomes.”
In collaboration with Dr. Bapat and other researchers in the lab, Ken was the first author on two studies published in the journals PLoS ONE (2009) and Laboratory Investigation (2010).
Ken will defend his thesis next year and will pursue post-doctoral Fellowship positions in Ontario to apply his expertise to new projects in the area of epigenetics.
Interest in cancer epigenetics was sparked initially in the 1970s, when early work in Europe suggested that changes in DNA methylation might be linked to aberrant gene expression in cancer. Soon after, researchers began to document abnormal DNA methylation in most kinds of cancer cells.
As the field of epigenetics widens, it is shedding new light on the underlying processes involved in cancer progression. Unlike genetic mutations, changes to a gene’s methylation can be reversed. For example, silenced tumour suppressor genes might be switched back on, through the use of approaches that lead to erasure of methyl groups from DNA.