Oncogenic Signaling Pathways in The Cancer Genome Atlas

By F. Sánchez-Vega, Marco Mina, J. Armenia, W. Chatila, Augustin Luna, Konnor C. La, Sofia G. Dimitriadoy, David L. Liu, H. Kantheti, Sadegh Saghafinia and 743 more. Cell, 2018

2,663 citations recorded by the source corpus.

Summary Genetic alterations in signaling pathways that control cell cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in 10 canonical pathways: cell cycle, Hippo, Myc, Notch, NRF2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, P53 and β-catenin/WNT. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy.

Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/a6d387a919008c9020673139877bd7ac5672d49f

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In Cancer Research

1. K. Guan
2. Matthew Meyerson
3. Oliver Stegle
4. Chad Creighton
5. Jakob Skou Pedersen
6. P. Oliver

In Oncology

1. K. Guan
2. Duojia Pan
3. Zemin Zhang
4. Z. Meng

Citations in the corpus

• The frequency of Ras mutations in cancer (2020, background): “All samples in TCGA have been subject to comprehensive genomic, epigenomic, transcriptomic, and proteomic analysis to better understand the oncogenic systems biology of molecular subtypes of cancer (37).”
• The Hippo Signaling Pathway in Development and Disease (2019, background): “Accordingly, the Cancer Genomic Atlas identified the Hippo pathway as one of the eight major signaling pathways commonly altered in human cancers (Sanchez-Vega et al., 2018).”
• ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020, background): “Investigating this dynamic interaction between convergent pro-inflammatory pathways, similar to what has been divulged in oncogenic pathways in cancer [193], will be key to understanding inappropriate inflammation in neurodegenerative disease.”
• Genomic basis for RNA alterations in cancer (2020, methodology): “For our pathway analysis, we used the TCGA pathway definitions to examine genes and pathways that have several alterations at both the DNA and RNA level 113 .”
• A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer (2019, background): “The pathologic conduit of different signaling pathways is sustained by genetic, transcriptomic, and epigenetic alterations with implications in different mechanisms, such as cellular fate [6,7,11,12].”
• The Hippo Pathway: Biology and Pathophysiology. (2019, background): “Recently, a systematic profiling of 9,125 tumor samples revealed a widespread dysregulation of Hippo pathway components in multiple human cancer types, including glioma, colorectal cancer, and endometrial cancer (160).”