0000000001304199

AUTHOR

Trinidad Caldés

Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer.

Exosome production from cancer-associated fibroblasts seems to be an important driver of tumor progression. We report the first in-depth biotype characterization of ncRNAs, analyzed by Next Generation Sequencing and Bioinformatics, expressed in established primary human normal and cancer-associated fibroblasts (CAFs) from cancer and normal mucosa tissues from 9 colorectal cancer patients, and/or packaged in their derived exosomes. Differential representation and enrichment analyses based on these ncRNAs revealed a significant number of differences between the ncRNA content of exosomes and the expression patterns of the normal and cancer-associated fibroblast cells. ncRNA regulatory elements…

research product

Additional file 1: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Supplementary material and methods. (DOCX 28 kb)

research product

Additional file 1 of Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Additional file 1.

research product

Additional file 14 of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

: Table S2. Target genes for CAF-EXO over-distributed sncRNAs supported by FDR

research product

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

Journal article TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ~480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10!-7), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10!-8) and BRCA1 mutation carrier (P = 1.1 × 10!-5) breast cancers and altered promot…

research product

Analysis ofBRCA1andBRCA2genes in Spanish breast/ovarian cancer patients: A high proportion of mutations unique to Spain and evidence of founder effects

We screened index cases from 410 Spanish breast/ovarian cancer families and 214 patients (19 of them males) with breast cancer for germ-line mutations in the BRCA1 and BRCA2 genes, using SSCP, PTT, CSGE, DGGE, and direct sequencing. We identified 60 mutations in BRCA1 and 53 in BRCA2. Of the 53 distinct mutations observed, 11 are novel and 12 have been reported only in Spanish families (41.5%). The prevalence of mutations in this set of families was 26.3%, but the percentage was higher in the families with breast and ovarian cancer (52.1%). The lowest proportion of mutations was found in the site-specific female breast cancer families (15.4%). Of the families with male breast cancer cases, …

research product

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This com…

research product

Reproductive and Hormonal Factors, and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Results from the International BRCA1/2 Carrier Cohort Study

Abstract Background: Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated in a small number of studies. Methods: We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox proportional hazards framework. Results: There were no significant differences in the risk of ova…

research product

Additional file 11: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Table S1. sncRNAs distributed differently in CAF-EXO samples from in NF-EXO ones. Highly significant lncRNAs and sncRNAs (FDR

research product

Additional file 8: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Mini web site presenting a dynamic venn diagram showing the relationships between the results cellular or exosomal over represented in the two analyses performed between NF- and CAF- exosomes. Clicking on any intersected number, the web site opens a dialog summarizing the ncRNAs species that correspond to the intersection. (ZIP 354 kb)

research product

Additional file 7: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Mini web site presenting a dynamic venn diagram intersecting the relationships of significance from the assayed ncRNAs in the differential expression analyses performed between NF- and CAF- exosomes versus their respective cellular environments (i.e. NF-CELL versus NF-EXO and CAF-CELL versus CAF-EXO). Clicking on any intersected number, the web site opens a dialog summarizing the ncRNAs species that correspond to the intersection. (HTML 120 kb)

research product

of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

research product

Additional file 5: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Excel file with two documents summarizing the results obtained from the differential expression NF-CELL versus NF-EXO analyses for differentially distributed lncRNAs and sncRNAs. (XLSX 73 kb)

research product

Additional file 12: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Excel document with two documents summarizing the results for the significant sncRNAs in the differential expression analysis between NF-EXO and CA-FEXO samples and target predictions for those significant in CAF-EXO samples (positive logFCs). (XLSX 292 kb)

research product

Additional file 3: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Excel document with the two count files used as input to EdgeR for differential expression analysis; one with the counts of reads of all samples mapped on the lncRNA references and another with the read counts of reads mapped on scnRNAs. (XLSX 221 kb)

research product

Additional file 9: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Excel file with two documents summarizing the results obtained from the differential expression NF-CELL versus CAF-CELL analyses for differentially expressed lncRNAs and sncRNAs. (XLSX 10 kb)

research product

Additional file 10: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Excel document with two documents summarizing the results for the significant lncRNAs in the differential expression analysis between NF-EXO and CAF-EXO samples and target predictions for those significant in CAF-EXO samples (positive logFCs). (XLS 40 kb)

research product

Additional file 4: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Figure S1. logFC-based MDS-plots (one for each type of lncRNA), where the first dimension corresponds to differences due to the type of sample (i.e. whether it is a normal cell, a tumor cell or an exosomal sample) and the second dimension corresponds to the differences between the samples themselves as biological replicates. The inferred dispersion and the Biological Coefficient of Variation (BCV) of all assayed samples for lncRNAs are 0.21201 and 0.4604, respectively, while the coefficients for sncRNA content are 0.25164 and 0.5016. These two coefficients reveal some interesting variation among samples. In this respect the multidimensional scaling (MDS) plots where the differences in ncRNA…

research product

Additional file 6: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Excel file with two documents summarizing the results obtained from the differential expression CAF-CELL versus CAF-EXO analyses for differentially distributed lncRNAs and sncRNAs. (XLSX 60 kb)

research product

Additional file 13 of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

: Multiple alignment of the 42 sncRNAs over represented in CAF-EXO samples. (FASTA 8 kb)

research product

Additional file 2: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

Absolute and average relative counts of reads mapped to each ncRNAs biotype per sample and fraction. (XLSX 15 kb)

research product

Additional file 15 of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer

: Figure S2. Heatmap with dendrogram showing the over-represented sncRNAs in CAF exosomes supported by FDRs below 1E-04 with the GO terms and metabolic pathways annotated to the predicted target genes summarized in Table 2. The number of target genes is used to color the breaks. If a sncRNA has no target gene assigned to a metabolic pathway (absence), the intersecting cell is colored white; if a ncRNA has one target gene assigned to a pathway, the cell is colored gray; and if more than two target genes are assigned to a pathway, it is colored black. The clustering was inferred by using the complete linkage with the Euclidean distance measure. (PNG 578 kb)

research product