Research output: Contribution to journal › Article › peer-review
Mutational signatures and mutable motifs in cancer genomes. / Rogozin, Igor B.; Pavlov, Youri I.; Goncearenco, Alexander et al.
In: Briefings in Bioinformatics, Vol. 19, No. 6, 30.05.2017, p. 1085-1101.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Mutational signatures and mutable motifs in cancer genomes
AU - Rogozin, Igor B.
AU - Pavlov, Youri I.
AU - Goncearenco, Alexander
AU - De, Subhajyoti
AU - Lada, Artem G.
AU - Poliakov, Eugenia
AU - Panchenko, Anna R.
AU - Cooper, David N.
N1 - Funding Information: The Intramural Research Program of the National Library of Medicine at the National Institutes of Health (to I.B.R., A.G. and A.R.P.); the National Institutes of Health Intramural Research Program of the National Eye Institute (to E.P.); Boettcher Foundation, American Cancer Society, P30 CA072720 (to S.D.); Nebraska Department of Health and Human Services LB506, grant 2017-48 (to Y.I.P.); and Qiagen Inc through a License Agreement with Cardiff University (to D.N.C.)
PY - 2017/5/30
Y1 - 2017/5/30
N2 - Cancer is a genetic disorder, meaning that a plethora of different mutations, whether somatic or germ line, underlie the etiology of the 'Emperor of Maladies'. Point mutations, chromosomal rearrangements and copy number changes, whether they have occurred spontaneously in predisposed individuals or have been induced by intrinsic or extrinsic (environmental) mutagens, lead to the activation of oncogenes and inactivation of tumor suppressor genes, thereby promoting malignancy. This scenario has now been recognized and experimentally confirmed in a wide range of different contexts. Over the past decade, a surge in available sequencing technologies has allowed the sequencing of whole genomes from liquid malignancies and solid tumors belonging to different types and stages of cancer, giving birth to the new field of cancer genomics. One of the most striking discoveries has been that cancer genomes are highly enriched with mutations of specific kinds. It has been suggested that these mutations can be classified into 'families' based on their mutational signatures. A mutational signature may be regarded as a type of base substitution (e.g. C:G to T:A) within a particular context of neighboring nucleotide sequence (the bases upstream and/or downstream of the mutation). These mutational signatures, supplemented by mutable motifs (a wider mutational context), promise to help us to understand the nature of the mutational processes that operate during tumor evolution because they represent the footprints of interactions between DNA, mutagens and the enzymes of the repair/replication/modification pathways.
AB - Cancer is a genetic disorder, meaning that a plethora of different mutations, whether somatic or germ line, underlie the etiology of the 'Emperor of Maladies'. Point mutations, chromosomal rearrangements and copy number changes, whether they have occurred spontaneously in predisposed individuals or have been induced by intrinsic or extrinsic (environmental) mutagens, lead to the activation of oncogenes and inactivation of tumor suppressor genes, thereby promoting malignancy. This scenario has now been recognized and experimentally confirmed in a wide range of different contexts. Over the past decade, a surge in available sequencing technologies has allowed the sequencing of whole genomes from liquid malignancies and solid tumors belonging to different types and stages of cancer, giving birth to the new field of cancer genomics. One of the most striking discoveries has been that cancer genomes are highly enriched with mutations of specific kinds. It has been suggested that these mutations can be classified into 'families' based on their mutational signatures. A mutational signature may be regarded as a type of base substitution (e.g. C:G to T:A) within a particular context of neighboring nucleotide sequence (the bases upstream and/or downstream of the mutation). These mutational signatures, supplemented by mutable motifs (a wider mutational context), promise to help us to understand the nature of the mutational processes that operate during tumor evolution because they represent the footprints of interactions between DNA, mutagens and the enzymes of the repair/replication/modification pathways.
KW - Cancer genomics
KW - Classification
KW - DNA sequence context
KW - Methylation
KW - Mutation spectra
KW - Somatic hypermutation
KW - Gene Expression
KW - Genetic Predisposition to Disease
KW - Genomics
KW - Humans
KW - Selection, Genetic
KW - Mutagens/pharmacology
KW - Neoplasms/genetics
KW - DNA/genetics
KW - DNA Methylation
KW - Models, Genetic
KW - Mutation
KW - Oncogenes
KW - Evolution, Molecular
UR - http://www.scopus.com/inward/record.url?scp=85057550637&partnerID=8YFLogxK
U2 - 10.1093/bib/bbx049
DO - 10.1093/bib/bbx049
M3 - Article
C2 - 28498882
AN - SCOPUS:85057550637
VL - 19
SP - 1085
EP - 1101
JO - Briefings in Bioinformatics
JF - Briefings in Bioinformatics
SN - 1467-5463
IS - 6
ER -
ID: 26153026