RNA components of the spliceosome regulate tissue- and cancer-specific alternative splicing RESEARCH

Alternative splicing of pre-mRNAs plays a pivotal role during the establishment and maintenance of human cell types. Characterizing the trans-acting regulatory proteins that control alternative splicing in both healthy and malignant cells has therefore been the focus of much research. Recent work has established that even core protein components of the spliceosome, which are required for splicing to proceed, can nonetheless contribute to splicing regulation by modulating splice site choice. We here demonstrate that the RNA components of the spliceosome likewise influence alternative splicing decisions and contribute to the establishment of global splicing programs. Although these small nuclear RNAs (snRNAs), termed U1, U2, U4, U5, and U6 snRNA, are present in equal stoichiometry within the spliceosome, we found that their relative levels vary by an order of magnitude during development, across tissues, and between normal and malignant cells. Physiologically relevant perturbation of individual snRNAs drove widespread gene-specific differences in alternative splicing, but not transcriptome-wide splicing failure. Genes that were particularly sensitive to variations in snRNA abundance in a breast cancer cell line model were likewise preferentially mis-spliced within a clinically diverse cohort of invasive breast ductal carcinomas. As aberrant mRNA splicing is prevalent in many solid and liquid tumors, we propose that a full understanding of dysregulated pre-mRNA processing in can...
Source: Genome Research - Category: Genetics & Stem Cells Authors: Tags: RESEARCH Source Type: research

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This 61-year-old woman presented with new primary triple negative breast cancer (TNBC) in the lateral breast 10 years after completing radiation for ductal carcinoma in situ (DCIS) in the same breast.1 Despite neoadjuvant chemotherapy and mastectomy with only residual DCIS and negative nodes, patient developed a TNBC re-recurrence only 9 months later. She was treated with chemotherapy, and there remains positive residual localized disease by positron emission tomography (PET). At this point we recommend the following.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Gray Zone Source Type: research
The objective of this study was to re-evaluate CD205 co-expression with other MEC markers, such as p63 and CD10, in nonneoplastic and neoplastic breast tissue and to evaluate its pathological diagnostic utility in these types of breast cancer. MATERIAL AND METHODS: Nonneoplastic breast tissue samples with a terminal duct lobular unit and duct were obtained from fibroadenoma and mastopathy patients. Neoplastic breast tissue samples included ductal carcinoma in situ (DCIS) (n=43) and invasive ductal carcinoma (IDC) (n=60), including the tubule-forming type (n=20). These specimens were investigated by CD205, p63, and CD10...
Source: Histology and Histopathology - Category: Cytology Tags: Histol Histopathol Source Type: research
Alternative splicing of pre-mRNAs plays a pivotal role during the establishment and maintenance of human cell types. Characterizing the trans-acting regulatory proteins that control alternative splicing has therefore been the focus of much research. Recent work has established that even core protein components of the spliceosome, which are required for splicing to proceed, can nonetheless contribute to splicing regulation by modulating splice site choice. We here show that the RNA components of the spliceosome likewise influence alternative splicing decisions. Although these small nuclear RNAs (snRNAs), termed U1, U2, U4, ...
Source: Genome Research - Category: Genetics & Stem Cells Authors: Tags: RESEARCH Source Type: research
ConclusionResults of our study highlighted the possible role of fat in breast cancer progression suggesting a negative prognostic value of IDFi.
Source: Pathology Research and Practice - Category: Pathology Source Type: research
AbstractPurposeNuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening.MethodsWe asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment.ResultsEleven screening programs reported 5068 screen-detected pure DCIS in nea...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
Objective To evaluate metabolic and volume-based parameters of 18-Fluorodeoxyglucose positron emission tomography/computed tomography ((18F)FDG PET/CT) for primary mass and axillary lymph node (ALN) metastasis in relation to molecular subtype, and immunohistochemistry and inflammatory markers in patients with invasive ductal carcinoma. Methods A total of 129 patients (mean±SD age: 49.2±13.0 years) with invasive ductal breast cancer who had (18F)FDG PET/CT imaging prior to chemotherapy or surgery were included in this single-center retrospective study. Data on patient age, molecular subtype, ALN metastasi...
Source: Nuclear Medicine Communications - Category: Nuclear Medicine Tags: Original Articles Source Type: research
CONCLUSIONS: Tumor-infiltrating lymphocytes are localized variously depending on the subtype. CD8+ CTLs were associated with a good prognosis, while FoxP3+ Tregs were associated with adverse outcomes in patients with breast cancer. CD8+ CTLs and FoxP3+ Tregs are potential predictive prognostic factors for patients with breast cancer. PMID: 31497220 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
A 35-year-old 30-week pregnant woman was referred to our institution for initial staging of a triple negative invasive ductal carcinoma of the left breast. To avoid fetal radiation exposure from CT, a whole-body 18F-FDG PET/MRI was performed. Simultaneous acquisition of PET, T1-, T2-, and diffusion-weighted sequences revealed left axillary node extension and no distant metastases. Fetal radiation dose was estimated at 1.9 mGy. Interestingly, low fetal brain uptake and high symmetrical myocardial metabolism in both ventricles were found. Delivery was induced at 37 weeks of amenorrhea, and the patient underwent 4 cycles of n...
Source: Clinical Nuclear Medicine - Category: Nuclear Medicine Tags: Interesting Images Source Type: research
Conditions:   Invasive Ductal Breast Carcinoma;   Invasive Ductal Carcinoma, Breast;   DCIS;   DCIS Grade 1;   DCIS Grade 2;   Breast Cancer Intervention:   Radiation: Accelerated Partial Breast Irradiation Sponsor:   Memorial Sloan Kettering Cancer Center Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Abstract Breast cancer is the most prevalent malignant tumor and main oncologic cause of mortality in women. Although most diagnosis of breast pathology is accomplished using hematoxylin and eosin stained sections, some cases require immunohistochemistry for proper evaluation. We investigated the latter cases including distinctions between ductal and lobular carcinoma, in situ and invasive carcinoma, typical ductal hyperplasia and atypical ductal hyperplasia/ductal carcinoma in situ, papillary and spindle cell lesion assessment, metastasis evaluation, and assessment of prognostic and therapy markers. E-cadherin is...
Source: Biotechnic and Histochemistry - Category: Research Authors: Tags: Biotech Histochem Source Type: research
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