Network of Cancer Genes explained

Network of Cancer Genes
Description:A web resource on systems-level properties of cancer genes
Organism:Homo sapiens
Center:Francis Crick Institute
Laboratory:Cancer Systems Biology Lab - Ciccarelli Lab
Released:May 2023
Url:http://www.network-cancer-genes.org/
Version:7.1

The Network of Cancer Genes (NCG) is a freely accessible web resource of genes that, when altered in their sequence, drive clonal expansion of normal tissues (healthy drivers) or cancer (cancer drivers). The project was launched in 2010 and has reached its 7th release in 2022. In 2023 the additional annotation of cancer drivers that interact with the tumour immune microenvironment (TIME drivers) was added. NCG7.1 reports information on 3,347 cancer drivers and 95 healthy drivers.[1] Of these, 596 are also TIME drivers.[2] NCG7.1 also reports the system-level properties and the associated publications of each driver, as well as a list possible false positives. NCG7.1 enables advanced searches on the primary anatomical site, cancer type, type of sequencing screens and literature supports.

Cancer drivers

A main feature of cancer cells is to acquire an unstable genome leading to genetic alterations that are major drivers of cancer evolution. NCG7.1 collects 591 well-known (canonical) and 2,756 candidate cancer drivers. These lists derive from the manual curation of 313 original publications, including 3 sources of canonical drivers [3] [4] [5] and 310 cancer sequencing screens. The latter describe whole genome or whole exome sequencing of cancer samples from a total of 41,780 patients from 122 different cancer types.

Healthy drivers

Recent technological advances have enabled detection of genomic instability also in healthy (non cancer) cells driving in situ formation of phenotypically normal clones.[6] [7] NCG7.1 collects 95 healthy drivers from 18 sequencing screens of healthy or diseased (non-cancer) tissues from 32,895 donors. Only 8 of these genes are not cancer drivers, suggesting a high overlap between genetic drivers of cancer and non-cancer evolution.[8]

TIME drivers

Cancer evolution occurs in a complex ecosystem formed of cancer and non-cancer cells that compose the tumour microenvironment (TME). An important component of the TME are immune cells, which may hamper or help tumour growth. Cancer cells engage in a dynamic crosstalk with the TIME that often involves cancer drivers. NCG7.1 annotates 596 that may impact on and be impacted by the TIME. Of these, 205 derive from the manual curation of the literature [9] [10] [11] [12] [13] and 391 are instead computationally predicted.

Systems level properties

Systems-level properties are properties of genes independent on an individual's gene function[14] Some of these properties can be used to distinguish cancer and healthy drivers from the rest of human genes.[15] The systems-level properties reported in NCG are:

Previous versions

External links

Notes and References

  1. Dressler . Lisa . Bortolomeazzi . Michele . Keddar . Mohamed Reda . Misetic . Hrvoje . Sartini . Giulia . Acha-Sagredo . Amelia . Montorsi . Lucia . Wijewardhane . Neshika . Repana . Dimitra . Nulsen . Joel . Goldman . Jacki . Pollitt . Marc . Davis . Patrick . Strange . Amy . Ambrose . Karen . 2022 . Comparative assessment of genes driving cancer and somatic evolution in non-cancer tissues: an update of the Network of Cancer Genes (NCG) resource . Genome Biology . en . 23 . 1 . 35 . 10.1186/s13059-022-02607-z . 1474-760X . 8790917 . 35078504 . free .
  2. Misetic . Hrvoje . Keddar . Mohamed Reda . Jeannon . Jean-Pierre . Ciccarelli . Francesca D. . 2023 . Mechanistic insights into the interactions between cancer drivers and the tumour immune microenvironment . en . 10.1101/2023.01.24.525325.
  3. Vogelstein . B. . Papadopoulos . N. . Velculescu . V. E. . Zhou . S. . Diaz . L. A. . Kinzler . K. W. . 2013 . Cancer Genome Landscapes . Science . en . 339 . 6127 . 1546–1558 . 10.1126/science.1235122 . 23539594 . 3749880 . 2013Sci...339.1546V . 0036-8075.
  4. Saito . Yuki . Koya . Junji . Araki . Mitsugu . Kogure . Yasunori . Shingaki . Sumito . Tabata . Mariko . McClure . Marni B. . Yoshifuji . Kota . Matsumoto . Shigeyuki . Isaka . Yuta . Tanaka . Hiroko . Kanai . Takanori . Miyano . Satoru . Shiraishi . Yuichi . Okuno . Yasushi . 2020 . Landscape and function of multiple mutations within individual oncogenes . Nature . en . 582 . 7810 . 95–99 . 10.1038/s41586-020-2175-2 . 32494066 . 2020Natur.582...95S . 256821260 . 0028-0836.
  5. Sondka . Zbyslaw . Bamford . Sally . Cole . Charlotte G. . Ward . Sari A. . Dunham . Ian . Forbes . Simon A. . 2018 . The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers . Nature Reviews Cancer . en . 18 . 11 . 696–705 . 10.1038/s41568-018-0060-1 . 30293088 . 6450507 . 1474-175X.
  6. Wijewardhane . Neshika . Dressler . Lisa . Ciccarelli . Francesca D. . 2021 . Normal Somatic Mutations in Cancer Transformation . Cancer Cell . en . 39 . 2 . 125–129 . 10.1016/j.ccell.2020.11.002. 33220180 . 227124230 .
  7. Kakiuchi . Nobuyuki . Ogawa . Seishi . 2021 . Clonal expansion in non-cancer tissues . Nature Reviews Cancer . en . 21 . 4 . 239–256 . 10.1038/s41568-021-00335-3 . 33627798 . 232049240 . 1474-175X.
  8. Acha-Sagredo . A. . Ganguli . P. . Ciccarelli . F.D. . 2022 . Somatic variation in normal tissues: friend or foe of cancer early detection? . Annals of Oncology . en . 33 . 12 . 1239–1249 . 10.1016/j.annonc.2022.09.156. 36162751 . 252501485 . free .
  9. Wellenstein . Max D. . de Visser . Karin E. . 2018 . Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape . Immunity . en . 48 . 3 . 399–416 . 10.1016/j.immuni.2018.03.004. 29562192 . 4130233 . free .
  10. Martin . Timothy D. . Patel . Rupesh S. . Cook . Danielle R. . Choi . Mei Yuk . Patil . Ajinkya . Liang . Anthony C. . Li . Mamie Z. . Haigis . Kevin M. . Elledge . Stephen J. . 2021-09-17 . The adaptive immune system is a major driver of selection for tumor suppressor gene inactivation . Science . 373 . 6561 . 1327–1335 . 10.1126/science.abg5784 . 34529489 . 2021Sci...373.1327M . 237547614 . 0036-8075.
  11. Mantovani . Alberto . Allavena . Paola . Sica . Antonio . Balkwill . Frances . 2008-07-24 . Cancer-related inflammation . Nature . en . 454 . 7203 . 436–444 . 10.1038/nature07205 . 18650914 . 2008Natur.454..436M . 2434/145688 . 0028-0836. free .
  12. Lawson . Keith A. . Sousa . Cristovão M. . Zhang . Xiaoyu . Kim . Eiru . Akthar . Rummy . Caumanns . Joseph J. . Yao . Yuxi . Mikolajewicz . Nicholas . Ross . Catherine . Brown . Kevin R. . Zid . Abdelrahman Abou . Fan . Zi Peng . Hui . Shirley . Krall . Jordan A. . Simons . Donald M. . 2020-10-01 . Functional genomic landscape of cancer-intrinsic evasion of killing by T cells . Nature . en . 586 . 7827 . 120–126 . 10.1038/s41586-020-2746-2 . 0028-0836 . 9014559 . 32968282. 2020Natur.586..120L .
  13. Dhainaut . Maxime . Rose . Samuel A. . Akturk . Guray . Wroblewska . Aleksandra . Nielsen . Sebastian R. . Park . Eun Sook . Buckup . Mark . Roudko . Vladimir . Pia . Luisanna . Sweeney . Robert . Le Berichel . Jessica . Wilk . C. Matthias . Bektesevic . Anela . Lee . Brian H. . Bhardwaj . Nina . 2022 . Spatial CRISPR genomics identifies regulators of the tumor microenvironment . Cell . 185 . 7 . 1223–1239.e20 . 10.1016/j.cell.2022.02.015 . 0092-8674 . 8992964 . 35290801.
  14. Ciccarelli. Francesca D.. 2010-06-11. The (r)evolution of cancer genetics. BMC Biology. 8. 1. 74. 10.1186/1741-7007-8-74. 1741-7007. 2883958. 20594288 . free .
  15. D'Antonio. Matteo. Ciccarelli. Francesca D.. 2013-05-29. Integrated analysis of recurrent properties of cancer genes to identify novel drivers. Genome Biology. 14. 5. R52. 10.1186/gb-2013-14-5-r52. 1474-760X. 4054099. 23718799 . free .
  16. Rambaldi. Davide. Giorgi. Federico M.. Capuani. Fabrizio. Ciliberto. Andrea. Ciccarelli. Francesca D.. 2008. Low duplicability and network fragility of cancer genes. Trends in Genetics. 24. 9. 427–430. 10.1016/j.tig.2008.06.003. 18675489. 0168-9525.
  17. Repana . Dimitra . Nulsen . Joel . Dressler . Lisa . Bortolomeazzi . Michele . Venkata . Santhilata Kuppili . Tourna . Aikaterini . Yakovleva . Anna . Palmieri . Tommaso . Ciccarelli . Francesca D. . 2019 . The Network of Cancer Genes (NCG): a comprehensive catalogue of known and candidate cancer genes from cancer sequencing screens . Genome Biology . en . 20 . 1 . 1 . 10.1101/389858 . 10.1186/s13059-018-1612-0 . 6317252 . 30606230 . free .
  18. An. Omer. Dall'Olio. Giovanni M.. Mourikis. Thanos P.. Ciccarelli. Francesca D.. 2016-01-04. NCG 5.0: updates of a manually curated repository of cancer genes and associated properties from cancer mutational screenings. Nucleic Acids Research. en. 44. D1. D992–D999. 10.1093/nar/gkv1123. 26516186. 4702816. 0305-1048.
  19. An. Omer. Pendino. Vera. D'Antonio. Matteo. Ratti. Emanuele. Gentilini. Marco. Ciccarelli. Francesca D.. 2014-01-01. NCG 4.0: the network of cancer genes in the era of massive mutational screenings of cancer genomes. Database. en. 2014. bau015. 10.1093/database/bau015. 3948431. 24608173.
  20. D'Antonio. Matteo. Pendino, Vera. Sinha, Shruti. Ciccarelli, Francesca D.. 2012. Network of Cancer Genes (NCG 3.0): integration and analysis of genetic and network properties of cancer genes. Nucleic Acids Res.. 40. Database issue. D978–83. 10.1093/nar/gkr952. 3245144. 22080562.
  21. Syed. Adnan S.. D'Antonio, Matteo. Ciccarelli, Francesca D.. 2010. Network of Cancer Genes: a web resource to analyze duplicability, orthology and network properties of cancer genes. Nucleic Acids Res.. 38. Database issue. D670–5. 10.1093/nar/gkp957. 2808873. 19906700.