Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1...

Descripción completa

Detalles Bibliográficos
Autores principales: Zaidi, Syed H., Harrison, Tabitha A., Phipps, Amanda I., Steinfelder, Robert, Trinh, Quang M., Qu, Conghui, Banbury, Barbara L., Georgeson, Peter, Grasso, Catherine S., Giannakis, Marios, Adams, Jeremy B., Alwers, Elizabeth, Amitay, Efrat L., Barfield, Richard T., Berndt, Sonja I., Borozan, Ivan, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D., Cao, Yin, Chan, Andrew T., Chang-Claude, Jenny, Connolly, Charles M., Drew, David A., Farris, Alton Brad, Figueiredo, Jane C., French, Amy J., Fuchs, Charles S., Garraway, Levi A., Gruber, Steve, Guinter, Mark A., Hamilton, Stanley R., Harlid, Sophia, Heisler, Lawrence E., Hidaka, Akihisa, Hopper, John L., Huang, Wen-Yi, Huyghe, Jeroen R., Jenkins, Mark A., Krzyzanowski, Paul M., Lemire, Mathieu, Lin, Yi, Luo, Xuemei, Mardis, Elaine R., McPherson, John D., Miller, Jessica K., Moreno, Victor, Mu, Xinmeng Jasmine, Nishihara, Reiko, Papadopoulos, Nickolas, Pasternack, Danielle, Quist, Michael J., Rafikova, Adilya, Reid, Emma E. G., Shinbrot, Eve, Shirts, Brian H., Stein, Lincoln D., Teney, Cherie D., Timms, Lee, Um, Caroline Y., Van Guelpen, Bethany, Van Tassel, Megan, Wang, Xiaolong, Wheeler, David A., Yung, Christina K., Hsu, Li, Ogino, Shuji, Gsur, Andrea, Newcomb, Polly A., Gallinger, Steven, Hoffmeister, Michael, Campbell, Peter T., Thibodeau, Stephen N., Sun, Wei, Hudson, Thomas J., Peters, Ulrike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371703/
https://www.ncbi.nlm.nih.gov/pubmed/32686686
http://dx.doi.org/10.1038/s41467-020-17386-z
Descripción
Sumario:Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0.42, 95% CI: 0.21–0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR = 1.53, 95% CI: 1.21–1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features.

Ejemplares similares