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2015 ; 4
(4
): 630-46
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Integrating Colon Cancer Microarray Data: Associating Locus-Specific Methylation
Groups to Gene Expression-Based Classifications
#MMPMID27600244
Barat A
; Ruskin HJ
; Byrne AT
; Prehn JH
Microarrays (Basel)
2015[Nov]; 4
(4
): 630-46
PMID27600244
show ga
Recently, considerable attention has been paid to gene expression-based
classifications of colorectal cancers (CRC) and their association with patient
prognosis. In addition to changes in gene expression, abnormal DNA-methylation is
known to play an important role in cancer onset and development, and colon cancer
is no exception to this rule. Large-scale technologies, such as methylation
microarray assays and specific sequencing of methylated DNA, have been used to
determine whole genome profiles of CpG island methylation in tissue samples. In
this article, publicly available microarray-based gene expression and methylation
data sets are used to characterize expression subtypes with respect to
locus-specific methylation. A major objective was to determine whether
integration of these data types improves previously characterized subtypes, or
provides evidence for additional subtypes. We used unsupervised clustering
techniques to determine methylation-based subgroups, which are subsequently
annotated with three published expression-based classifications, comprising from
three to six subtypes. Our results showed that, while methylation profiles
provide a further basis for segregation of certain (Inflammatory and Goblet-like)
finer-grained expression-based subtypes, they also suggest that other
finer-grained subtypes are not distinctive and can be considered as a single
subtype.