Project description:Overabundance of circulating RNY transcripts and fragments has been associated with cancer. Here we analyzed the levels of RNYs in plasma collected from women before developing breast cancer and compared the results to matched controls that remained unaffected. Using small RNA-seq, two cohorts were analyzed: a cohort of women carriers of pathogenic variants in BRCA1 and BRCA2, and diagnosed with breast cancer as a first neoplasm within a period of < 12 months after blood test (n = 11), or that provided a blood sample at a similar age and remained unaffected (n = 13); and a cohort from a long-term prospective study, and comprising 8 sporadic breast cancer cases (diagnosed in a period of < 12 months after blood test) and 8 controls matched for individual and epidemiological variables
Project description:The Susan G. Komen Tissue Bank at Indiana University Simon Cancer Center (KTB) is the only repository of normal breast tissues donated by healthy women. As expected, a relatively small number of KTB donors (≈5%) diagnosed with breast cancer a few years post-donation. The specimens originally donated by these women (here labeled “susceptible normal tissue”) provide a window into the earliest phases of breast cancer development. Here, we investigated the transcriptomic changes in the histologically normal breast tissues donated by women 2-8 years prior to their diagnosis of breast cancer (mostly DCIS), as compared with breasts from age-matched healthy subjects.
Project description:The Susan G. Komen Tissue Bank at Indiana University Simon Cancer Center (KTB) is the only repository of normal breast tissues donated by healthy women. As expected, a relatively small number of KTB donors (≈5%) diagnosed with breast cancer a few years post-donation. The specimens originally donated by these women (here labeled “susceptible normal tissue”) provide a window into the earliest phases of breast cancer development. Here, we investigated the DNA metylation changes in the histologically normal breast tissues donated by women 2-8 years prior to their diagnosis of breast cancer (mostly DCIS), as compared with breasts from age-matched healthy subjects.
Project description:Liquid biopsy is noninvasive and convenient to detect cancer-derived materials in blood or other body fluids. The aim of this study was to identify tRNA-derived small RNAs (tsRNAs) in plasma that could distinguish patients with breast cancer (BC) from healthy controls. Basing on high-throughput sequencing, 15 significantly upregulated tsRNAs were selected and assessed in cell supernatants and cell lines. 6 tsRNAs were identified and verified in a large cohort of 120 patients with BC and 112 healthy controls. tRF-Arg-CCT-017, tRF-Gly-CCC-001 and tiRNA-Phe-GAA-003 could serve as novel diagnostic biomarkers. Meanwhile, tRF-Arg-CCT-017 and tiRNA-Phe-GAA-003 could also act as prognostic biomarkers. Target genes of these tsRNAs were related to the development of cancer. These results suggest that specific tsRNAs in plasma might serve as diagnostic and prognostic biomarkers of BC.
Project description:We report the sequencing of small RNAs present in the plasma of three normal subjects. In addition to microRNAs we identified abundant non-human small RNA sequences. The organisms from which these were derived were identified by BLAST searches with contigs assembled from the short sequences. The taxonomic profiles were very consistent between individuals, including plants and microbes reported previously in the microbiome, but in proportions distinct from other sites. The majority of bacterial reads were from the phylum Proteobacteria, whilst for 5 of 6 individuals over 90% of the more abundant fungal reads were from the phylum Ascomycota; of these over 90% were from the order Hypocreales. Most reads mapped to rRNA sequences and the presence of specific common sequences was confirmed by RT-PCR. In addition, extremely abundant small RNAs derived from human Y RNAs were detected. We conclude that a characteristic profile of a subset of the human microbiome can be obtained by sequencing small RNAs present in the blood. The origin and potential function of these molecules remains to be determined, but the specific profile is likely to reflect health status. This facile test has immense potential to provide biomarkers for the diagnosis and prognosis of human disease. The profile of small RNAs present in the plasma of three normal subjects was determined