A multidimensional analysis of genes mutated in breast and colorectal cancers.
A recent study of a large number of genes in a panel of breast and colorectal cancers identified somatic mutations in 1149 genes. To identify potential biological processes affected by these genes, we examined their putative roles based on sequence similarity, membership in known functional groups and pathways, and predicted interactions with other proteins. These analyses identified functional groups and pathways that were enriched for mutated genes in both tumor types. Additionally, the results pointed to differences in molecular mechanisms that underlie breast and colorectal cancers, including various intracellular signaling and metabolic pathways. These studies provide a multidimensional framework to guide further research and help identify cellular processes critical for malignant progression and therapeutic intervention.
Lin
Jimmy
J
Ludwig Center for Cancer Genetics and Therapeutics, and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21231, USA.
Gan
Christine M
CM
Zhang
Xiaosong
X
Jones
Siân
S
Sjöblom
Tobias
T
Wood
Laura D
LD
Parsons
D Williams
DW
Papadopoulos
Nickolas
N
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Parmigiani
Giovanni
G
Velculescu
Victor E
VE
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D009363:Neoplasm Proteins
Nature. 2007 Apr 12;446(7137):765-70
17429393
Nat Genet. 2000 May;25(1):25-9
10802651
Cell. 2002 Oct 4;111(1):41-50
12372299
Genome Biol. 2003;4(3):R22
12620107
Science. 2003 Dec 5;302(5651):1727-36
14605208
Nat Rev Cancer. 2004 Feb;4(2):106-17
14732865
Science. 2004 Jan 23;303(5657):540-3
14704431
In Silico Biol. 2004;4(1):5-6
15089749
Nat Med. 2004 Aug;10(8):789-99
15286780
J Mol Biol. 1990 Oct 5;215(3):403-10
2231712
Nucleic Acids Res. 1999 Jan 1;27(1):29-34
9847135
Genome Biol. 2004;5(12):R101
15575967
Carcinogenesis. 2005 Jul;26(7):1241-6
15790588
Nature. 2000 Feb 10;403(6770):623-7
10688190
Cancer Causes Control. 2006 May;17(4):525-30
16596306
Nucleic Acids Res. 2001 Jan 1;29(1):37-40
11125043
J Biol Chem. 2000 Dec 29;275(52):40710-7
11018029
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4569-74
11283351
Cancer Metastasis Rev. 2006 Mar;25(1):9-34
16680569
Bioinformatics. 2006 Sep 15;22(18):2291-7
16844706
Science. 2006 Oct 13;314(5797):268-74
16959974
Int J Hematol. 2005 Jul;82(1):21-7
16105755
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13544-9
16174746
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
16199517
Nat Rev Drug Discov. 2007 May;6(5):373-90
17464296