M**1
发帖数: 162 | 1 What's called somatic mutation? Thanks! | a*****x
发帖数: 901 | | l**********1
发帖数: 5204 | 3 LZ pls try go to
//www.sanger.ac.uk/genetics/CGP/cosmic/
or Cell article:
by
Nik-Zainal S et al. and Stratton MR (2012)
Mutational processes molding the genomes of 21 breast cancers.
Cell. 149: 979-93.
Abstract
All cancers carry somatic mutations. The patterns of mutation in cancer
genomes reflect the DNA damage and repair processes to which cancer cells
and their precursors have been exposed. To explore these mechanisms further,
we generated catalogs of somatic mutation from 21 breast cancers and
applied mathematical methods to extract mutational signatures of the
underlying processes. Multiple distinct single- and double-nucleotide
substitution signatures were discernible. Cancers with BRCA1 or BRCA2
mutations exhibited a characteristic combination of substitution mutation
signatures and a distinctive profile of deletions. Complex relationships
between somatic mutation prevalence and transcription were detected. A
remarkable phenomenon of localized hypermutation, termed "kataegis," was
observed. Regions of kataegis differed between cancers but usually
colocalized with somatic rearrangements. Base substitutions in these regions
were almost exclusively of cytosine at TpC dinucleotides. The mechanisms
underlying most of these mutational signatures are unknown. However, a role
for the APOBEC family of cytidine deaminases is proposed.
//www.ncbi.nlm.nih.gov/pubmed/22608084
Statistical Analysis
Mutational processes were extracted by using nonnegative matrix
factorization.
Monte Carlo simulations were performed to assess how randomly
distributed mutations differed to the primary cancer genomes. A Kolmogorov-
Smirnov test
was used to compare the distribution of indels mediated
by repeats or microhomology.
Ps: 近来 Cell 上以Biostasitic analysis by Monte Carlo simulations or
Hidden Markov Model 的solid key data 越来越多了 哈 |
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