Milestones in Cancer Genetic Discoveries

1974: The nuclear matrix is identified as the site for DNA replication, shedding light on cellular changes that cause cancer

1983: Discovery that changes in DNA methylation, now called epigenetic changes, are found in cancers, including early cancers

1984: Discovery that chromosome 11p changes are integral to the development of pediatric kidney cancers called Wilms’ tumor

1987: Discovery of GLI genes and their link to brain tumors

1988: A now-classic paper published in the New England Journal of Medicine presents the idea that cancers result from the sequential mutations of oncogenes and tumor suppressor genes  

1989: Discovery of mutations in the p53 gene in human colorectal cancers, that it is a tumor suppressor gene and that p53 genes are common denominators of most common human tumor types. It is now known that TP53 is the most highly mutated tumor suppressor gene in cancer

1990: Discovery of the biochemical mechanisms through which p53 suppresses tumor development

1991: Discovery of the APC gene, and that inherited mutations in the gene are responsible for the cancer predisposition syndrome called familial adenomatous polyposis (FAP) and  that mutations in APC initiate virtually all colorectal tumors, with or without hereditary predisposition

1992: Discovery that genetic alterations, such as mutations, can be found in the stool of people with colorectal cancer, leading to the first genetic test approved by the FDA for detecting early cancers and creating the paradigm for liquid biopsies

1993: Discovery of gene (MSH2) is responsible for a major inherited cancer syndrome, hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome and discovery of the biochemical mechanisms through which APC suppresses tumor development   

1994: Discovery of mismatch repair genes, such as MLH1, responsible for cases of HNPCC not caused by mutations in MSH2 

Discovery of a technique, Serial Analysis of Gene Expression, to evaluate all the genes transcribed in a normal or tumor cell, coining the word “transcriptome”

1992–1999: Discovery of now widely used tests to determine whether patients have inherited mutations responsible for FAP or HNCPCC

1995: ScienceWatch names cancer genetics pioneer Bert Vogelstein as the most frequently cited scientist in the world in all fields of science

1999: FLT3 gene is cloned and linked to a type of leukemia, with drugs developed to target the mutation along with tests to confirm the drugs hit their genetic target

Discovery of chromosomal instability as a major underlying feature of most cancers

2002: First gene mutation in prostate cancer is discovered

2004: Discovery of mutations in PIK3CA in colon, breast, stomach, brain and other cancers. Later found to be the most highly mutated oncogene in cancer, paving the way for targeted drugs — now widely used — for the treatment of breast cancers with PIK3CA mutations

2006: First analysis of all of the genes in colon and breast cancers, establishing the paradigm for modern cancer genetic research and defining “cancer genome landscapes”

2008–2010: First analysis of all of the genes in pancreas, brain, ovarian and other cancer types

Discovery of the IDH1 and IDH2 genes, establishing the importance of mutations in genes that control metabolism, leading to now widely used drugs that target these mutations in brain tumors and leukemias

2009: The first use of genome-wide sequencing to identify a gene that causes a hereditary disease — in this case, pancreatic cancer

2010: Discovery that the interval from the first, initiating mutation in a tumor cell to the development of a cancer is 20–30 years, providing a broad window for detection and prevention

2011–2018: Discovery of the genetic alterations that drive various types of pancreatic cysts

2012: The genetic driver of hereditary prostate cancer is identified

Resistance mutations are found in blood of patients shortly after treatment, marking cancers predestined to recur

2013–2018: Development of DNA-based tests on urine, saliva and Pap smears that can detect early cancers of the bladder, head and neck, and uterus

2017: Discovery that patients with mutations in the mismatch repair genes MSH2 or MLH1 in their cancers are extraordinarily responsive to treatment with immune checkpoint inhibitors, leading to the first FDA approval of a drug to treat a patient on the basis of the genetic alterations within a tumor, regardless of the tumor type  

Study reveals genomic roots of many ovarian tumors is in the fallopian tubes

Discovery of a new type of cancer drug, called MANAbodies, that uses the genetic mistakes inside cancer cells to generate an immune response

2018: Multicancer blood tests are developed and shown to detect relatively early-stage cancers in a noninvasive fashion, laying the foundation for an immense amount of academic and industry research to develop “liquid biopsies” for cancer screening

2019: The largest pancreatic cancer genome-wide association study discovers changes to five new regions in the human genome that may increase the risk of pancreatic cancer

Development of a test that distinguishes precancerous pancreatic cysts that require surgery from harmless benign cysts

2021: Discovery of new immunotherapy approaches for treating people with cancer based on the genetic alterations found in their tumors, such as those in p53

2022: Successful clinical trial shows that DNA shed from early-stage colon cancer into bloodstream can be used to manage patients after surgery