Comparing mutation patterns across cancer
Breast 2022 estimated U.S. annual incidence: 287,850 new cases and 43,250 deaths A majority of breast tumors contains mutations in a category of genes that regulate when cells divide. This includes the genes CCND1, ERBB2, FGFR1 and PIK3CA . The mutations often result in proteins that continually signal for cell growth and division. Fortunately, approved drugs now exist that target many of these genetic mutations.
The Cancer Genome Atlas analyzed the genetic changes present in over 3,000 tumors from 12 different cancer types. Alterations were consistently identified in over 479 regions of the genome.
2.7 %
151 areas that were frequently deleted in tumors
31.5 %
13 genes that were silenced by DNA overmethylation
116 regions that were amplified, meaning additional copies
199 individual genes that were mutated across
24.2 %
multiple cancers
Ovarian 2022 estimated U.S. annual incidence: 19,880 new cases and 12,810 deaths
41.5 %
of genes were likely present in the cancer cells
A two-tier classification system was recently introduced for ovarian cancer. Low grade tumors are generally slow-growing and have a more favorable outcome. Approximately two-thirds have mutations in the BRAF, ERBB2 or KRAS genes. In contrast, high-grade ovarian cancer devel- ops rapidly and nearly all cases have mutations not only in the TP53 gene, but also show gains and losses in large chunks of genetic material throughout the genome.
The various mutations and alterations can be loosely grouped into one of four major biological pathways: two involved in receiving and trans- mitting “grow” signals from outside the cell, one that oversees DNA replication and cell division, and one that searches for and repairs DNA damage. Mutations within the same pathway are common to many tumor types. Additionally, most cancers have a combination of mutations that impacted multiple pathways. Classification of genetic alterations
Percentage of Tumors with Mutations in the DNA Repair Pathway
0% 20% 40% 60% 80% 100%
Colorectal 2022 estimated U.S. annual incidence: 106,180 new cases Most colorectal cancers arise through a stepwise accumulation of genetic mutations that occur over the span of many years. Commonly, mutations arise in genes such as AKT1, BRAF, KRAS, PIK3CA, PTEN and SMAD4 . Many of these are targets for small molecule drugs. A significant fraction of col- orectal cancers have mutations in the sys- tem that monitors and repairs DNA damage. Not surprisingly, these cancer cells have an unusually high frequency of mutation across their genome.
Genetic Mutations Across Multiple Cancer-causing Pathways
100%
80%
60%
40%
20%
0%
CHART TO RIGHT REFERENCES: Ciriello G, et al. Nature Genetics 45:1127-1135 (2013). Garraway L.A., Journal of Clinical Oncology 15:1806-1814 (2013). Lim, D. and Oliva, E. Pathology 45:229-242 (2013). Nana-Sinkam, S.P. and Powell, C.A. Chest 143 (supplement): e30S-e39S.
no pathways mutated 1 pathways mutated
2 pathways mutated
3 pathways mutated
4 pathways mutated
Tumors with mutations in the four pathways
15
15
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