Advancing Patient-Centric Genomic Medicine
Advancing Patient-Centric Genomic Medicine
As outlined by the National Cancer Institute, The Cancer Genome Atlas (TCGA) is a large-scale pilot project, carried out in collaboration with the National Human Genome Research Institute for the purpose of furthering our understanding of the molecular basis of cancer through the application of genome analysis technologies, including but not limited to identifying mutations in DNA sequence, copy number variation, and alterations in methylation status. Squamous cell carcinoma of the lung is one of the three target diseases that are being studied in this pilot project. In this issue of ONCOLOGY, Devarakonda and colleagues discuss the recently reported TCGA study, in which 178 tumor samples and matched normal tissue samples were subjected to whole exome and transcriptome sequencing. It is clear that rapid progress is being made in the field of molecular diagnostics, which provides a powerful new approach that can help us better understand how cancers develop. The technology platforms to sequence the human genome are in a dizzying phase of innovation.
As we attempt to apply this explosion of information to specific clinical settings, we need to consider the critical issue of how to obtain the specimens that are urgently needed for continued genetic research and development of personalized medicine, while simultaneously maintaining rigorous respect for the donors of these specimens. The recent furor over the public posting of genetic data from the HeLa cell line can serve as a cautionary tale. Over 60 years ago, scientists took a tissue specimen of an aggressive cervical cancer from a young African American woman, Henrietta Lacks, without her knowledge or permission. This specimen was the genesis of the first human cancer-cell line, called HeLa, which has been widely used by researchers around the world. When the HeLa genome was posted on an open-access database earlier this year, although the action broke no law nor violated any protocol, it did upset the Lacks family, since the sequence can reveal heritable aspects of the family’s DNA. It wasn’t until August that the National Institutes of Health and the Lacks family reached an agreement as to how the genomic data might be used by researchers going forward. While in many ways the situation involving the Lacks family and their genomic data is unique, we must keep in mind that information about donors and their kin can often be deduced even from so-called “de-identified” data.
Sorting out the clinical implications of genomic data is going to require extensive or perhaps remarkably extensive clinical correlations; obtaining these clinical data will require the cooperation of our patients. Thus, we have to redouble our efforts to partner with our patients to engage them in our mutual journey of discovery—but in doing so, we must take the Lacks story to heart. The nature and magnitude of observed molecular changes in cancer suggest that an extremely complex and context-specific regulatory control process is warranted.
To sort out the molecular complexity of cancer so that we can define the critical targets needed to develop drugs that arrest cancer progression—that is a shared challenge. While it may seem premature to some, the time to more broadly discuss the issue of consent to obtain needed clinical specimens is now. We currently have tools that are going to allow us to understand aspects of diseases in ways that we cannot yet fully articulate, but we need specimens and associated clinical data to proceed. If we outline this prospect carefully to our patients, we may respectfully ask them to work with us on a journey to develop the tools to reduce the health burden of cancer. Perhaps not all will give their consent, but it is very likely that donation of clinical information will not be our limiting factor in our pursuit of approaches that will finally control squamous cell lung cancer and other lethal cancers.
1. Devarakonda S, Morgensztern D, Govindan R. Clinical applications of The Cancer Genome Atlas (TCGA) Project for squamous cell lung carcinoma. Oncology (Williston Park). 2013;27:899-906.
2. Hammerman PS, Hayes DN, Wilkerson MD, et al. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489:519-25.
3. Hudson KL, Collins FS. Biospecimen policy: family matters. Nature. 2013;500:141-2.