Editing Malignant transformation (section)

===Mutations===

One underlying commonality in cancers is genetic mutation, acquired either by inheritance, or, more commonly, by mutations in one's [[somatic (biology)|somatic]] [[DNA]] over time.  The mutations considered important in cancers are those that alter protein coding genes (the [[exome]]).  As Vogelstein et al. point out, a typical tumor contains two to eight exome "driver gene" mutations, and a larger number of exome mutations that are "passengers" that confer no selective growth advantage.<ref name="pmid23539594">{{cite journal |vauthors=Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW |title=Cancer genome landscapes |journal=Science |volume=339 |issue=6127 |pages=1546–58 |year=2013 |pmid=23539594 |pmc=3749880 |doi=10.1126/science.1235122 |bibcode=2013Sci...339.1546V }}</ref>

Cancers also generally have [[genome instability]], that includes a high frequency of mutations in the [[noncoding DNA]] that makes up about 98% of the human genome.  The average number of DNA sequence mutations in the entire genome of breast cancer tissue is about 20,000.<ref name="pmid22492626">{{cite journal | author = Yost SE | author2 = Smith EN | author3 = Schwab RB | author4 = Bao L | author5 = Jung H| author6 = Wang X | author7 = Voest E | author8 = Pierce JP | author9 = Messer K| author10 = Parker BA | author11 = Harismendy O| author12 = Frazer KA | title = Identification of high-confidence somatic mutations in whole genome sequence of formalin-fixed breast cancer specimens | journal = Nucleic Acids Res. | volume = 40 | issue = 14 | pages = e107 |date=August 2012 | pmid = 22492626 | pmc = 3413110 | doi = 10.1093/nar/gks299 }}</ref>  In an average melanoma (where melanomas have a higher [[exome]] mutation frequency<ref name="pmid23539594"/>) the total number of DNA sequence mutations is about 80,000.<ref name="pmid22622578">{{cite journal | author = Berger MF | author2 = Hodis E | author3 = Heffernan TP | author4 = Deribe YL | author5 = Lawrence MS | author6 = Protopopov A | author7 = Ivanova E | author8 = Watson IR | author9 = Nickerson E | author10 = Ghosh P | author11 = Zhang H| author12 = Zeid R | author13 = Ren X| author14 = Cibulskis K | author15 = Sivachenko AY| author16 = Wagle N | author17 = Sucker A| author18 = Sougnez C | author19 = Onofrio R| author20 = Ambrogio L | author21 = Auclair D| author22 = Fennell T | author23 = Carter SL| author24 = Drier Y | author25 = Stojanov P | author26 = Singer MA | author27 = Voet D | author28 = Jing R | author29 = Saksena G| author30 = Barretina J | author31 = Ramos AH | author32 = Pugh TJ | author33 = Stransky N | author34 = Parkin M | author35 = Winckler W| author36 = Mahan S | author37 = Ardlie K| author38 = Baldwin J | author39 = Wargo J| author40 = Schadendorf D | author41 = Meyerson M| author42 = Gabriel SB| author43 = Golub TR| author44 = Wagner SN| author45 = Lander ES| author46 = Getz G| author47 = Chin L| author48 = Garraway LA | title = Melanoma genome sequencing reveals frequent PREX2 mutations | journal = Nature | volume = 485 | issue = 7399 | pages = 502–6 |date=May 2012 | pmid = 22622578 | pmc = 3367798 | doi = 10.1038/nature11071 | bibcode = 2012Natur.485..502B }}</ref>