Aligning Germline Cancer Predisposition With Tumor-Based Next-Generation Sequencing for Modern Oncology Diagnosis, Interception, and Therapeutic Development.
Timothy A Yap, Zsofia K Stadler, Leigh Anne Stout, Bryan P Schneider
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引用次数: 1
Abstract
In the era of precision medicine, genomic interrogation for identification of both germline and somatic genetic alterations has become increasingly important. While such germline testing was usually undertaken via a phenotype-driven single-gene approach, with the advent of next-generation sequencing (NGS) technologies, the widespread utilization of multigene panels, often agnostic of cancer phenotype, has become a commonplace in many different cancer types. At the same time, somatic tumor testing in oncology performed for the purpose of guiding therapeutic decisions for targeted therapies has also rapidly expanded, recently starting to incorporate not just patients with recurrent or metastatic cancer but even patients with early-stage disease. An integrated approach may be the best approach for the optimal management of patients with different cancers. The lack of complete congruence between germline and somatic NGS tests does not minimize the power or importance of either, but highlights the need to understand their limitations so as not to overlook an important finding or omission. NGS tests built to more uniformly and comprehensively evaluate both the germline and tumor simultaneously are urgently required and are in development. In this article, we discuss approaches to somatic and germline analyses in patients with cancer and the knowledge gained from integration of tumor-normal sequencing. We also detail strategies for the incorporation of genomic analysis into oncology care delivery models and the important emergence of poly(ADP-ribose) polymerase and other DNA Damage Response inhibitors in the clinic for patients with cancer with germline and somatic BRCA1 and BRCA2 mutations.
期刊介绍:
The Ed Book is a National Library of Medicine–indexed collection of articles written by ASCO Annual Meeting faculty and invited leaders in oncology. Ed Book was launched in 1985 to highlight standards of care and inspire future therapeutic possibilities in oncology. Published annually, each volume highlights the most compelling research and developments across the multidisciplinary fields of oncology and serves as an enduring scholarly resource for all members of the cancer care team long after the Meeting concludes. These articles address issues in the following areas, among others: Immuno-oncology, Surgical, radiation, and medical oncology, Clinical informatics and quality of care, Global health, Survivorship.