Transcription profiling of breast tumors and surrounding tissue to detect pre-malignant histological and genetic changes
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Cheng AS
PROVIDER: S-ECPF-TABM-276 | biostudies-other | 2008 Mar
REPOSITORIES: biostudies-other
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Project description:The aim of our study is to examine the region of tissue surrounding or adjacent to breast tumor in order to detect pre-malignant histological and genetic changes that may be predictive of risk of breast cancer. In this study, histological and gene expression data of breast tissue were obtained from patients that underwent mastectomy at various stages of breast carcinoma. For each patient, samples were obtained from the tumor region and four surrounding zones (1cm, 2cm, 3 cm and 4 cm away from the grossly visible tumor boundary), where possible. We have also breast samples from healthy individuals undergoing breast reduction surgery (mammoplasty). Microarray gene expression profiles of tissue samples (tumor and surrounding tissue, and breast reduction mammoplasty) was performed. In addition pathologist reviewed all slides to provide a details histology of all samples (excluding breast mammoplasty)
2008-04-13 | E-TABM-276 | biostudies-arrayexpress
Project description:Enlargement of normal terminal duct lobular units (TDLUs) by hyperplastic columnar epithelial cells is one of the most common abnormalities of growth in the adult female human breast. These hyperplastic enlarged lobular units (HELUs) are important clinically as the earliest histologically identifiable potential precursor of breast cancer. The causes of the hyperplasia are unknown but may include estrogen-simulated growth mediated by estrogen receptor alpha, which is highly elevated in HELUs and may be fundamental to their development. This study used DNA microarray technology and RNA from microdissected pure epithelial cells to learn more about changes in gene expression and molecular pathways associated with the development of HELUs from TDLUs Experiment Overall Design: Samples for the microarray studies were derived from 8 formalin-fixed paraffin-embedded tissue (FFPET) biopsies containing paired normal TDLUs and well-developed HELUs from non-cancerous adult female human breasts obtained within the past 3 years. Populations of nearly pure (>95%) epithelial cells were isolated from the TDLUs and HELUs in each biopsy (approximately 25,000 cells/sample) by laser capture microdissection (LCM)
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Project description:Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. Overexpression of several genes may be a result of surgical trauma or preoperative manipulation, and may not reflect any biological impact of the disease. This study compares the expression profiles in preoperative tissue while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery.
| S-ECPF-MTAB-469 | biostudies-other
Project description:Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. Overexpression of several genes may be a result of surgical trauma or preoperative manipulation, and may not reflect any biological impact of the disease. This study compares the expression profiles in preoperative tissue while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery.
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Project description:Primary malignant melanoma of esophagus is very rare, and its clinicopathologic and genetic features have not been extensively investigated. In this study, 20 tumors from 14 male and 6 female patients (40-79 years old) were evaluated. Dysphagia, chest pain, and weight loss were frequent symptoms. Thirteen melanomas, including two with multiple lesions, involved the distal third of esophagus. The median tumor diameter was 6 cm. Epithelioid morphology, moderate atypia, and pigmentation were typical findings. None of the patients had melanoma elsewhere, and all tumors exhibited a junctional peri-epithelial component consistent with a primary lesion. The median mitotic activity was 11 per 10 high-power fields (range, 0-31). Nine patients died of tumor within 4-22 months, however, two showed long-term (96 and 104 months) survival. In 15 cases, tissue for further immunohistochemical and molecular studies were available. BRAF, KIT, and NRAS mutation status was assessed by Sanger sequencing in all 15 tumors. The next-generation sequencing of 50 or 409 genes was performed in five and three cases, respectively. IGF1R expression indicating activation of the IGF axis was seen in 82% (9/11) of tumors. However, no BRAF mutations were identified. In 33% (5/15) of tumors, NRAS mutations were detected. KIT expression was seen in 50% (7/14) of melanomas including single KIT mutant. Two of three tumors evaluated with 409 genes panel revealed multiple driver mutations indicating sub-clonal expansion, whereas a single mutation (TSC1 p.H371Q) was the sole change in the third case. SF3B1 p.K666T and p.R625C mutations were detected in two cases. However, no co-occurrence of SF3B1 and GNAQ or GNA11 mutations, seen in uveal melanoma, was detected. FBXW7 p.R465C and p.R479G mutations, linked to cancer progression, were found in two of eight tumors. In summary, esophageal melanoma mutation profile indicates complexity of molecular mechanisms underlying its pathogenesis.
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Project description:BackgroundDue to the low incidence and histological heterogeneity, the molecular features and underlying carcinogenic mechanisms of thymic epithelial tumors (TETs) are yet to be fully elucidated, especially for different subtypes of TETs.MethodsTumor tissue samples of 43 TETs with distinct histological subtypes were collected. We analyzed the molecular characteristics in different subtypes based on whole exome sequencing data.ResultsThe mutational profiles of the different subtypes of TETs varied. Compared with thymomas, thymic carcinomas (TCs) had a higher mutation frequency of MYO16 (33% vs. 3%, p = 0.024) and a lower frequency of ZNF729 mutations (0% vs. 35%, p = 0.044). No significant difference was observed in the median tumor mutation burden across different subtypes. The value of copy number variation burden, weighted genome instability index, and the number of amplified segments were all higher in TCs than thymomas, and they also tended to be higher in B3 thymoma than in non-B3 thymomas, while they had no significant differences between B3 thymoma and TCs. Clustering analyses revealed that Wnt, MAPK, Hedgehog, AMPK, and cell junction assembly signaling pathways were exclusively enriched in non-B3 thymomas, lysine degradation pathway in B3 thymoma, and extracellular matrix-receptor (ECM-receptor) interaction, positive regulation of cell cycle process, and activation of innate immune response pathways in TCs.ConclusionsThis study revealed distinct molecular landscapes of different subtypes of TETs, suggesting diverse pathogenesis of non-B3 thymomas, B3 thymomas, and TCs. Our findings warrant further validation in future large-scale studies and may provide a theoretical basis for potential personalized therapeutic strategies.
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Project description:Gene expression profiling in 50 glial brain tumors and 4 normal brains using 42,000-feature cDNA microarrays (from total RNA). Tumors: 50 fresh-frozen glioma specimens subjected to standard WHO classification. Specimens included astrocytic [2 juvenile pilocytic astrocytomas, 1 low-grade astrocytic glioma, 1 anaplastic astrocytomas, 31 glioblastomas (of these 2 secondary glioblastomas and 2 gliosarcomas)], oligodendroglial [5 oligodendrogliomas, 3 anaplastic oligodendrogliomas], and 6 anaplastic oligoastrocytomas tumors. One tumor had been classified as glioneuronal neoplasm. Normal brain was purchased from Stratagene. Stratagene Universal Common Reference was used as reference RNA. The results provide insights into molecular mechanisms and pathways associated with gliomagenesis.
| S-ECPF-SMDB-3152 | biostudies-other
Project description:BackgroundThe incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice.MethodsIn this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay.ResultsFor each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84-0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82-0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82-0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value?>?0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47-0.99) for identifying the tumor origins.ConclusionsThe 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.
| S-EPMC7846996 | biostudies-literature
Project description:BACKGROUND:Systematic cancer screening has led to the increased detection of pre-malignant lesions (PMLs). The absence of reliable prognostic markers has led mostly to over treatment resulting in potentially unnecessary stress, or insufficient treatment and avoidable progression. Importantly, most mutational profiling studies have relied on PML synchronous to invasive cancer, or performed in patients without outcome information, hence limiting their utility for biomarker discovery. The limitations in comprehensive mutational profiling of PMLs are in large part due to the significant technical and methodological challenges: most PML specimens are small, fixed in formalin and paraffin embedded (FFPE) and lack matching normal DNA. METHODS:Using test DNA from a highly degraded FFPE specimen, multiple targeted sequencing approaches were evaluated, varying DNA input amount (3-200 ng), library preparation strategy (BE: Blunt-End, SS: Single-Strand, AT: A-Tailing) and target size (whole exome vs. cancer gene panel). Variants in high-input DNA from FFPE and mirrored frozen specimens were used for PML-specific variant calling training and testing, respectively. The resulting approach was applied to profile and compare multiple regions micro-dissected (mean area 5 mm2) from 3 breast ductal carcinoma in situ (DCIS). RESULTS:Using low-input FFPE DNA, BE and SS libraries resulted in 4.9 and 3.7 increase over AT libraries in the fraction of whole exome covered at 20x (BE:87%, SS:63%, AT:17%). Compared to high-confidence somatic mutations from frozen specimens, PML-specific variant filtering increased recall (BE:85%, SS:80%, AT:75%) and precision (BE:93%, SS:91%, AT:84%) to levels expected from sampling variation. Copy number alterations were consistent across all tested approaches and only impacted by the design of the capture probe-set. Applied to DNA extracted from 9 micro-dissected regions (8 PML, 1 normal epithelium), the approach achieved comparable performance, illustrated the data adequacy to identify candidate driver events (GATA3 mutations, ERBB2 or FGFR1 gains, TP53 loss) and measure intra-lesion genetic heterogeneity. CONCLUSION:Alternate experimental and analytical strategies increased the accuracy of DNA sequencing from archived micro-dissected PML regions, supporting the deeper molecular characterization of early cancer lesions and achieving a critical milestone in the development of biology-informed prognostic markers and precision chemo-prevention strategies.
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Project description:We used microarrays to identify the expression differences of FKBP5 gene between the pancreatic tumor and normal samples. On average normal samples had more FKBP5 expression compared to tumor samples .Experiment Overall Design: This experiment consists of 36 tumor samples and 16 normal samples; a total of 52 samples. 16 samples consist of both tumor and normal expression data, whereas 20 samples consist of only tumor data.
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