We have developed and validated for the diagnosis of inherited colorectal cancer (CRC) a massive parallel sequencing strategy based on: (i) fast capture of exonic and intronic sequences from ten genes involved in Mendelian forms of CRC (MLH1, MSH2, MSH6, PMS2, APC, MUTYH, STK11, SMAD4, BMPR1A and PTEN); (ii) sequencing on MiSeq and NextSeq 500 Illumina platforms; (iii) a bioinformatic pipeline that includes BWA-Picard-GATK (Broad Institute) and CASAVA (Illumina) in parallel for mapping and variant calling, Alamut Batch (Interactive BioSoftware) for annotation, CANOES for CNV detection and finally, chimeric reads analysis for the detection of other types of structural variants (SVs).
These results suggest that PTEN plays a significant pathogenic role in both HNPCC and sporadic endometrial carcinogenesis, unlike the scenarios for colorectal cancer.
Furthermore, we observed a strong association between PIK3CA mutations and MSI status (P=0.0046) while PTEN loss was more frequent in microsatellite stable (MSS) CRC (P=0.043).
MiR-17-5p is a predictive factor for chemotherapy response and a prognostic factor for overall survival in CRC, which is due to its regulation of PTEN expression.
MicroRNA-32 (miR-32) is upregulated in colorectal cancer (CRC) tissues; its overexpression leads to increased cell proliferation, migration and invasion, as well as reduced apoptosis of CRC cells, at least partly by inhibiting the target gene phosphatase and tensin homolog.
In the current study, we sought to determine the relationship of PTEN mutation, 10q23 loss of heterozygosity, PTEN expression, and MSI status in colorectal cancers (CRCs).
Conversely, PTEN protein expression was markedly lower in CRC compared with adjacent normal tissues. p‑4E‑BP1 protein upregulation tissues samples was consistent with PTEN downregulation in CRC samples. p‑4E‑BP1 overexpression was predominant in patients with metastasis to the regional lymph nodes.
The expression of miR-181A and PTEN in CRC patients with late liver metastases was higher than that of the normal (control) group, whereas the expression of miR-181A and PTEN was lower in all pathological groups (TNM I-TNM IV).
When the mRNA levels of the primary tumors were compared by tumor location, only PTEN mRNA expression differed significantly between left and right-sided CRC (median PTEN expression: left 1.00 vs. right 1.68; p = 0.017).
Our data demonstrated that suppression of miR-29a enhanced PTEN expression, inhibited cancer cell proliferation, facilitated apoptosis, and weakened drug resistance, which provides academic basis for the treatment of colorectal cancer.
The levels of mir-21 did not associate with the expression of PTEN, an important tumour suppressor in CRC and one of many putative targets of miR-21, but interestingly was associated with stage of disease in the PTEN expressing tumours.
We hypothesized that alternative mechanisms of PTEN allelic inactivation, such as promoter hypermethylation, might be operative in CRC and that PTEN inactivation may be related to recognized forms of genomic instability.
Interestingly, PTEN can also exert some biological functions independently of its catalytic activity.A feature of colorectal cancers is the relatively low incidence of PTEN mutation or deletion, whereas PTEN downregulation occurs in approximately one third of tumours.
We analysed the mutation status in KRAS, BRAF and PIK3CA and PTEN expression in two separate CRC cohorts, Northern Sweden Health Disease Study (NSHDS; n=197) and Colorectal Cancer in Umeå Study (CRUMS; n=414).
Mutations of KRAS, NRAS, BRAF, and phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and deregulation of PTEN expression influence the responsiveness against anti-EGFR therapy in colorectal carcinomas.