Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer

Abstract

We found that gene-expression profiles enabled stratification of CRC patients into four subgroups. The efficacy of anti-EGFR therapy was correlated with component 1 from PCA. This comprehensive study may explain the heterogeneity of unresectable advanced or recurrent CRC and could be useful for identifying novel biomarkers for CRC treatment.

Exome sequencing characterizes the somatic mutation spectrum of early serrated lesions in a patient with serrated polyposis syndrome (SPS)

“…Thus, other alterations such as specific epigenetic changes, in particular hypermethylation of tumour suppressor genes, or mutations in regulatory regions, which result in aberrant expression, might be the major driving force of tumour progression in sporadic and syndromic serrated polyps as proposed by other investigators [ 15 , 32 , 45 ]. This would be consistent with the recent observation that aberrant crypt foci (ACF) as the earliest precancerous lesions of the serrated pathway, arise by a BRAF mutation and methylation of a few genes and develop into SSP/As through accumulated methylation of a limited number of additional genes [ 15 , 36 ].…”

“…Further genetic alterations which have been described in more advanced tumours include targets of MSI ( BAX, TGFßR2, IGFR2 , p53, often present late during adenoma/carcinoma progression), CDKN2A / p16 , MINT genes, 3p, and 15q (CRAC1) [ 10 , 33 , 44 ]. Consistently, it was shown that the number of methylated genes increased significantly in the order of aberrant crypt foci (ACF) to SSA/P to serrated cancer [ 36 ].…”

“…Afterwards, 123 genes which had been proposed as driver candidate genes of the serrated pathway due to genetic alterations or epigenetic silencing in serrated lesions, including established causative genes or candidate genes for (hereditary) colorectal tumours (Additional file 1 : Table S1) [ 19 , 29 – 36 ] were analyzed for the presence of any rare variant.…”

Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer

“…Gene expression analysis was performed by the Whole Human Genome 4 × 44 K Microarray (Agilent Technologies, Santa Clara, CA, USA) using the same method as that used by Inoue et al [ 41 ]. All gene expression analyses were conducted at our laboratory.…”

“…Target enrichment was performed using SureSelect ™ XT Human All Exon V5 + lncRNA (Agilent Technologies, Santa Clara, CA, USA) according to the manufacturer’s protocol on the Illumina HiSeq 2000/2500 platform. For the other 106 cases, direct DNA sequencing of KRAS (codons 12 and 13) and BRAF (codon 600) was performed using the method described by Inoue et al [ 41 ]. Among the 106 cases, infrequent- RAS mutations, including KRAS (codons 61 and 146) and NRAS (codons 12, 13, and 61), were additionally analyzed in 28 cases using Luminex Assay, and the other 28 cases were analyzed using direct DNA sequencing.…”