This week's edition of PLOS Medicine, featuring four Research Articles and two Perspectives, begins a special issue devoted to research on cancer genomics. Research and discussion papers selected along with two leaders in the field, Guest Editors Elaine Mardis and Marc Ladanyi, will highlight progress in the study of important cancer types, and assess the clinical implications of progress in this fast-moving field.
In their Perspective article, James Topham and Marco Marra discuss the acquisition of genetic information from tumors, which in recent years has progressed from localized analyses of single genes, and subsequently panels of genes, that are important in specific cancer types, to whole-genome sequencing. Intensive effort is being applied to analyses of tumor genomes aimed at selection of appropriate therapies for individual patients, and the authors emphasize the need to study the dynamic nature of tumor genome sequences — which can change over time and adapt to cytotoxic and other treatments — to maximize the potential benefit for patients.
In a Research Article, Dr. Charles Perou of the University of North Carolina's Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA and colleagues study the evolution of tumors in two patients with triple-negative, basal-like breast cancer, a disease associated with lack of estrogen receptor, progesterone receptor, and HER2 which generally results in poor clinical outcome. For many cancer types, it is the metastases, or the spread of cancer cells from the original tumor to other parts of the body, that are life-threatening, and it is therefore of interest to study the cancer after it has left the site of origin. The researchers studied whole-genome sequence and gene expression information from primary tumors and metastases obtained from the patients at autopsy, and report similar somatic mutation and copy number patterns across all tumors in an individual patient. This analysis identified multiple populations of cells, or clones, in the original tumor as well as in the metastatic sites. The findings suggest that metastatic potential is established early in the trajectory of this form of breast cancer, and that multiple clones from the primary tumor traveled together to distant organs.
Anindya Dutta and colleagues present a study of gene expression changes in large datasets derived from patients with brain tumors in a second Research Article — focusing on low-grade gliomas and glioblastoma multiforme, which is a particularly intractable form of the disease. The authors study expression of large numbers of long noncoding RNAs (lncRNAs), which are thought to be involved in governing the expression of other genes and thereby controlling important processes such as development and tumorigenesis. The authors found that a signature made up of selected lncRNAs was associated with length of survival in patients with low-grade gliomas. If validated in future work, these findings could lead to a way to estimate prognosis for patients with this type of tumor, which might be useful in planning treatment.
Further research and discussion articles addressing important topics in the area of cancer genomics will appear throughout the December, 2016 issue of PLOS Medicine.
No specific funding received for this article.
The authors have declared that no competing interests exist.
Topham JT, Marra MA (2016) Sequencing Strategies to Guide Decision Making in Cancer Treatment. PLoS Med 13(12): e1002189. doi:10.1371/journal.pmed.1002189
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada, Department of Medical Genetics, University of British Columbia, Vancouver, Canada
IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002189
Research Article (1)
This study was supported by funds from the following sources: the Breast Cancer Research Foundation (LAC); the National Institutes of Health (NIH) (LAC, M01RR00046); National Cancer Institute P50-CA58223 Breast SPORE Program (LAC); National Cancer Institute P50-CA58223 Breast SPORE Program (CMP); National Cancer Institute R01-CA195754-01 (CMP); National Cancer Institute R01-CA148761 (CMP); the Breast Cancer Research Foundation (CMP); National Cancer Institute F30-CA200345 (MBS); and the National Human Genome Research Institute Center Initiated Projects U54HG003079 (ERM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
I have read the journal's policy and the authors of this manuscript have the following competing interests: CMP is an equity stock holder of BioClassifier LLC and University Genomics, and ERM, CMP, and JSP have filed a patent on the PAM50 subtyping assay. ERM served as guest editor on PLOS Medicine's Special Issue on Cancer Genomics.
Hoadley KA, Siegel MB, Kanchi KL, Miller CA, Ding L, Zhao W, et al. (2016) Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases. PLoS Med 13(12): e1002174. doi:10.1371/journal.pmed.1002174
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America McDonnell Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America Department of Mathematics, Washington University in St. Louis, St. Louis, Missouri, United States of America Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002174
Research Article (2)
The study was funded by the National Cancer Institute grants P01 CA104106 and R01 CA166054 to AD. BJR was supported by training grants T32 GM007267 and T32 CA009109. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The authors have declared that no competing interests exist.
Reon BJ, Anaya J, Zhang Y, Mandell J, Purow B, Abounader R, et al. (2016) Expression of lncRNAs in Low-Grade Gliomas and Glioblastoma Multiforme: An In Silico Analysis. PLoS Med 13(12): e1002192. doi:10.1371/journal.pmed.1002192
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America Department of Biochemistry, University of Virginia, Charlottesville, Virginia, United States of America Division of Neuro-Oncology, Neurology Department, University of Virginia Health System, Old Medical School, Charlottesville, Virginia, United States of America
IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002192
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