Cancer Genetics Overview

Principles

Definition

Cancer genetics is the academic field dedicated to investigating the genetic and genomic alterations underlying cancer initiation, development, and progression. This research encompasses the study of somatic and germline mutations, chromosomal changes, and epigenetic modifications, providing critical insights for understanding cancer biology and informing diagnostic and therapeutic approaches.

Ontological type

Core Concepts

Clinical Applications

Genetic Mechanisms

Key developments

Key Figures

Oncogene Molecular Era era

In the Oncogene Molecular Era (1977-1983), J. Michael Bishop and Harold Varmus established the proto-oncogene concept, showing that normal cellular genes resemble viral oncogenes and can be converted to transforming genes. Peter D. Vogt mapped viral oncogenes across Rous sarcoma virus and related retroviruses, demonstrating how specific gene alterations produce transforming activity and hinting at cellular homologs. Michael Wigler and colleagues pioneered cloning and sequencing of mammalian oncogenes, notably isolating ras family members and showing they encode transforming p21 proteins. Robert Weinberg and collaborators linked Ras family mutations to human cancers, revealing recurrent point mutations in tumor samples and establishing mutation-driven oncogenesis as a central cancer mechanism.

Driver Discovery and Classification era

P. Andrew Futreal [1] is a pivotal figure in cancer genomics during this era, with affiliations at the Institute of Cancer Research [3] and Stanford University [4]. His key contributions in this era include mutations of the BRAF gene in human cancer [6], as described in Mutations of the BRAF gene in human cancer [6] (2002), and signatures of mutational processes in human cancer [7], as detailed in Signatures of mutational processes in human cancer [7] (2013), which reframed cancer around genomic drivers and mutational landscapes. Michael R. Stratton [2] is another central figure of this era, with affiliations at the Institute of Cancer Research [3] and Johns Hopkins University [5]. His contributions include the discovery of mutations of the BRAF gene in human cancer [6], as reported in Mutations of the BRAF gene in human cancer [6] (2002), and the characterization of signatures of mutational processes in human cancer [7], as described in Signatures of mutational processes in human cancer [7] (2013), which together anchored driver-focused classification in this era.

Biomarker-Driven Precision Oncology era

Janis M. Taube [1], affiliated with Johns Hopkins University [3] and University of Washington [4], has been instrumental in advancing biomarker-driven cancer biology in this era. Her key contribution, highlighted by the 2017 paper Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade [6], is the identification that mismatch repair deficiency can predict response to PD-1 blockade [6], underpinning the biomarker-driven immunotherapy paradigm across diverse cancers. Drew M. Pardoll [2], affiliated with Harvard University [5] and Johns Hopkins University [3], has been a central figure in shaping this era. His contributions include articulating that genomic repair deficiencies can predict response to PD-1 blockade [6], thereby catalyzing a biomarker-led immunotherapy paradigm central to this era.