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PLOS BLOGS Speaking of Medicine

Introducing a Special Issue of PLOS Medicine: Clinical Implications of Cancer Genomics

Senior Editor Richard Turner discusses the contents of the Cancer Genomics Special Issue’s first week.

This month, PLOS Medicine’s content is devoted entirely to our special issue on the clinical implications of cancer genomics—two leading experts, Guest Editors Elaine Mardis and Marc Ladanyi, have advised us on the selection of research papers and on commissioning discussion pieces. This research and commentary material will aim to highlight progress in study of the genomics of important cancer types, assess the clinical implications of progress in this fast-moving field, and look ahead to what benefits future research may bring.

The first week of the special issue features two Perspectives and four Research Articles. In their introductory Perspective, James Topham and Marco Marra discuss the acquisition of genetic information about tumors, which in recent years has progressed dramatically from localized analyses of single genes, through panels of genes that are important in specific cancer types, and most recently to whole-genome sequencing endeavors. Intensive effort is now being applied to analyses of tumor genomes aimed at selection of appropriate therapies for identifiable subgroups of patients, and several research studies in the special issue will reflect this approach. The authors emphasize the need to study the plasticity of tumor genome sequences—which can change over time and adapt to cytotoxic and other therapies—to optimize potential benefits for patients.

Charles Swanton and colleagues report in their Research Article on a phase 2 clinical trial comprising women with HER2-positive inflammatory breast cancer, an aggressive but rare form of the disease. Although recruitment to the trial was halted following discouraging findings in another trial investigating the drug of interest, afatinib, Swanton and colleagues’ study included planned analyses of tumor genome sequences before and after afatinib treatment. The results indicate a high mutational burden in this type of breast cancer, which could provide clues to future investigations of tailored treatment. In an accompanying Perspective, Francisco Beca and Andrew Beck comment that, via “sequencing individual tumors within the course of treatment, we will gain a deeper understanding of how inflammatory breast cancer responds and progresses in individual patients, which may lead to better and safer therapies tailored to the dynamic genomic evolution of an individual patient’s disease”.

In a second Research Article, Charles Perou and colleagues study the progression and migration of tumors in two patients with so-called triple negative or basal-like breast cancer, a disease that is associated with a lack of biomarkers which can be used to guide treatment, and with poor clinical outcome. In many forms of cancer it is secondary tumors, or metastases, that are life-threatening, and it is therefore important to study the spread of cancer beyond 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 when comparing tumors in an individual patient. Multiple different subpopulations of cells, or clones, were observed in both primary tumors and metastases. The findings suggest that genetic changes are established early in the trajectory of this form of breast cancer, but that multiple clones can populate metastases originating from the primary tumor.

Anindya Dutta and colleagues present a study of gene expression changes in large datasets derived from patients with brain tumors in a further Research Article—addressing low-grade gliomas and glioblastoma multiforme, an especially intractable disease entity. 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 and thereby inform treatment planning for patients with this type of tumor.

In the week’s final Research Article, Maria Teresa Landi and colleagues present a genomic analysis of lung adenocarcinomas based on EAGLE, a detailed long-term study of patients with lung cancer carried out in Italy with the aim of characterizing genetic and behavioral factors (in addition to tobacco smoking) associated with the disease. The authors describe two new driver genes in their study which, together with information about patterns of somatic mutations in the tumors analysed, provide information on tumorigenic processes in this common disease inviting further study.

The research studies published this week underline the rapid methodological progress that has redefined understanding of tumor genomes, and illustrate the richness and complexity of the data that are becoming available. Breast cancer research is strongly represented, as expected given the comparatively advanced understanding of biomarkers and treatment targets in this group of diseases, but progress is also evident in other forms of cancer contributing substantially to overall disease burden. Although much of the research is translational in nature and focuses on modestly sized patient cohorts, such studies can be very valuable in charting future experimental and clinical directions.

Further articles will appear throughout the December 2016 issue of PLOS Medicine, and the second week will include studies on a newly defined subtype of triple negative breast cancer, and on histological transformation and progression of follicular lymphoma. To view all papers as they publish, go to the Special Issue collection each Tuesday this month.


Featured Image Credit: tungsten_snaps, Flickr.

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