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BCRF Grantee Since

2005

Donor Recognition

The Tanger Outlets Award

Area(s) of Focus

Katherine L. Nathanson, MD

Associate Professor
Co-Leader, Cancer Control and Prevention Program
Chief Oncogenomics Physician
Director of Genetics, Basser Center for BRCA Research
Abramson Family Cancer Research Institute
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania

Current Research

Using massively parallel sequencing, Dr. Nathanson is taking several approaches to better understand the genetics of high risk women without BRCA1/2 mutations. She and her team have been doing targeted sequencing of known breast cancer susceptibility genes in women with early onset breast cancer, women with multiple primary breast and ovarian cancers, and those with breast cancer and multiple affected family members. They have performed whole exome (most of the coding regions in the genome) sequencing on high risk breast cancer families and patients with breast and ovarian cancer, and targeted (specific genes) sequencing in women with early onset breast cancer before age 40. In women from high risk families and with multiple primary cancers, Dr. Nathanson and colleagues have identified previously unknown causative mutations in genes associated with breast cancer susceptibility explaining the breast and/or ovarian cancer risk in the individual or family. They also have identified variation in novel genes, which may be associated with cancer susceptibility. They are working with other BCRF investigators to select genes and put together a sample set, for validation of these novel findings. In the women with breast cancer under age 40, these investigators have found preliminarily that ~10% carry deleterious mutations (known to affect protein function), most in moderate penetrance genes. These results are of particular importance, as similar testing is being offered commercially. This study is the first step in clinical translation, as we need to understand the range and types of mutations identified in women with different disease characteristics. Dr. Nathanson’s team is also collaborating on studies that investigate how to give results back to patients so that they best understand them.

In the coming year, Dr. Nathanson plans to expand to include women with multiple other primary cancers. In collaboration with Drs. Fergus Couch and Kenneth Offit, her group has identified novel breast cancer susceptibility genes of interest, which they collectively will take into validation into a series of high risk breast cancer cases and controls.

Mid-Year Summary

Dr. Nathanson’s team has performed whole exome (most of the coding regions in the genome) sequencing on high risk breast cancer families and patients with breast and ovarian cancer, and targeted (specific genes) sequencing in women with early onset breast cancer before age 40. In the 277 women with breast cancer under age 40, they have found preliminarily that ~8% carry deleterious mutations (known to affect protein function). Most of these mutations are in moderate penetrance genes, which currently are not clinically actionable, and only 1% have mutations in genes that are considered clinically actionable. In women from high risk families and those with both breast and ovarian cancer independent of family history, they identify mutations in moderate penetrance genes in ~11%. These results are of particular importance, as similar testing is being offered commercially. This study is the first step in clinical translation, as the researchers need to understand the range and types of mutations identified in women with different disease characteristics. They are collaborating on studies that investigate how to give results back to patients so that they best understand them. They also have identified variation in novel genes, which may be associated with cancer susceptibility. Together with other BCRF investigators they are in the process of validating these novel findings.

Bio

Dr. Nathanson is an Associate Professor in the Division of Translational Medicine and Human Genetics in the Department of Medicine and Co-Leader of the Cancer Control Program in the Abramson Cancer Center at the University of Pennsylvania. She received her medical degree from the University of Pennsylvania School of Medicine. Dr. Nathanson trained in Internal Medicine at Beth Israel Hospital, Boston and in Clinical Genetics at the University of Pennsylvania School of Medicine. Dr. Nathanson is a cancer geneticist, boarded in Internal Medicine and Clinical Genetics; she both runs a research laboratory and has a busy clinical practice. She runs a translational research laboratory and has had a long term interest and published extensively on breast cancer genetics on topics including the identification of novel breast cancer susceptibility genes, characterization of cohorts that carry mutations in BRCA1/2 and genetic modifiers of breast cancer penetrance in BRCA1/2 mutation carriers, among others. Dr. Nathanson supervises multiple massively parallel sequencing projects in her laboratory to investigate both the inherited and somatic genetics of cancer.

She also is a key contributor to the development of a large collection of DNA and tissue samples from high-risk family breast cancer cohorts, participating in several national and international consortium, including the Consortium of Identifiers of Modifiers of BRCA1/2 (CIMBA) and Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA). Dr. Nathanson has published in multiple high impact journals and serves on several editorial boards, including being the Cancer Genetics editor for Genetics in Medicine. She also serves on committees for several national professional societies, such as ACGME and ACMG, and serves as a member of national review committees, including the National Institutes of Health Cancer Genetics study section.

Co-Investigators