Proteomic profiling of soft tissuesarcomas with SWATH mass spectrometry
Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers. While large-scale genomic and epigenomic profiling of STS have been undertaken, proteomic analysis has thus far been limited. Here we utilise sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for proteomic profiling of formalin fixed paraffin embedded (FFPE) specimens from a cohort of STS patients (n = 36) across four histological subtypes (leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma).
We quantified 2951 proteins across all cases and show that there is a significant enrichment of gene sets associated with smooth muscle contraction in leiomyosarcoma, RNA splicing regulation in synovial sarcoma and leukocyte activation in undifferentiated pleomorphic sarcoma.
We further identified a subgroup of STS cases that have a distinct expression profile in a panel of proteins, with worse survival outcomes when compared to the rest of the cohort. Our study highlights the value of comprehensive proteomic characterisation as a means to identify histotype-specific STS profiles that describe key biological pathways of clinical and therapeutic relevance; as well as for discovering new prognostic biomarkers in this group of rare and difficult-to-treat diseases.
Novel Morphologic Findings in PLAG1-Rearranged Soft TissueTumors
Oncogenesis in PLAG1-rearranged tumors often results from PLAG1 transcription factor overexpression driven by promoter-swapping between constitutively expressed fusion partners. PLAG1-rearranged tumors demonstrate diverse morphologies. This study adds to this morphologic heterogeneity by introducing two tumors with PLAG1 rearrangements that display distinct histologic features. The first arose in the inguinal region of a 3-year-old, appeared well-circumscribed with a multinodular pattern, and harbored two fusions: ZFHX4-PLAG1 and CHCHD7-PLAG1.
The second arose in the pelvic cavity of a 15-year-old girl, was extensively infiltrative and vascularized with an adipocytic component, and demonstrated a COL3A1-PLAG1 fusion. Both showed low-grade cytomorphology, scarce mitoses, no necrosis, and expression of CD34 and desmin. The ZFHX4-/CHCHD7-PLAG1-rearranged tumor showed no evidence of recurrence after 5 months.
By contrast, the COL3A1-PLAG1-rearranged tumor quickly recurred following primary excision with positive margins; subsequent re-excision with adjuvant chemotherapy resulted in no evidence of recurrence after two years. While both tumors show overlap with benign and malignant fibroblastic and fibrovascular neoplasms, they also display divergent features. These cases highlight the importance of appropriate characterization in soft tissue tumors with unusual clinical and histologic characteristics. This article is protected by copyright. All rights reserved.
CancerSeq™ Plus Paraffin Tissue Tumor Sections: Thyroid
DNA Methylation in Ovarian Tumors-a Comparison Between Fresh Tissue and FFPE Samples
Among women, ovarian cancer (OC) is one of the most severe forms of malignancy, accounting for a low 5-year survival rate, of approximately 52%. Early symptoms are unspecific and hence hard to detect. The origin of OC and its subtypes are still unclear, underlying the need for efficient diagnostic biomarkers. In that regard, epigenetics studies are emerging in cancer diagnostics, with encouraging outcomes.
Among them, DNA methylation profiling has shown that the origins of the cancer epigenome are associated with molecular factors that are crucial to carcinogenesis, such as regulation of oncogenes and tumor suppressors.
Furthermore, those events have been detected in abnormal cell morphology before neoplastic formation, indicating its potential crucial use in the OC diagnostics in the future. Nonetheless, studies are limited, and whether methylation analysis can be performed optimally in formalin-fixed paraffin-embedded (FFPE) preparations of OC cases is still elusive.
In the present report, we investigated the performance of DNA methylation analysis in FFPE samples, compared to their matched fresh frozen tissue in a small cohort of OC samples.
We found that the overall DNA methylation profile in FFPE tissue showed high concordance to that found in fresh frozen tissue, and accounting for the small cohort size, the differentially methylated sites found primarily in frozen tissue, compared to benign samples, were also reproducible in FFPE.
Overall, by using samples from our current clinical setting of tissue preservation, these preliminary observations might provide insights into the clinical use of FFPE tissues in methylation studies without critically compromising the outcome.
An atlas of the tissue and blood metagenome in cancer reveals novel links between bacteria, viruses and cancer
Background: Host tissue infections by bacteria and viruses can cause cancer. Known viral carcinogenic mechanisms are disruption of the host genome via genomic integration and expression of oncogenic viral proteins. An important bacterial carcinogenic mechanism is chronic inflammation. Massively parallel sequencing now routinely generates datasets large enough to contain detectable traces of bacterial and viral nucleic acids of taxa that colonize the examined tissue or are integrated into the host genome. However, this hidden resource has not been comprehensively studied in large patient cohorts.
Methods: In the present study, 3025 whole-genome sequencing datasets and, where available, corresponding RNA-seq datasets are leveraged to gain insight into novel links between viruses, bacteria, and cancer. Datasets were obtained from multiple International Cancer Genome Consortium studies, with additional controls added from the 1000 genome project.
A customized pipeline based on KRAKEN was developed and validated to identify bacterial and viral sequences in the datasets. Raw results were stringently filtered to reduce false positives and remove likely contaminants.
Results: The resulting map confirms known links and expands current knowledge by identifying novel associations. Moreover, the detection of certain bacteria or viruses is associated with profound differences in patient and tumor phenotypes, such as patient age, tumor stage, survival, and somatic mutations in cancer genes or gene expression profiles.
Conclusions: Overall, these results provide a detailed, unprecedented map of links between viruses, bacteria, and cancer that can serve as a reference for future studies and further experimental validation. Video Abstract.
Description: Esophageal cancer tissue array with esophagus tissue as control, including TNM, clinical stage and pathology grade, 48 cases/ 48 cores, replacing ES482
Description: Our tissue products are produced by strictly following the IRB ethical standards and procedures and from highest quality tissues. Immediately after collection the tissues are placed in liquid nitrogen and examined by certified pathologists. The thickness of each individual section is ~5um. They are Hematoxylin and Eosin stained and quality tested by immunostaining with anti-beta-actin antibodies. Our tissue products are suitable for various studies on cellular level (RNA localization, Protein expression, etc.) on both normal and pathological cases. It is also an excellent control and educational tool.
Description: Esophagus tissue and esophagus cancer tissue array, including pathology grade, TNM and clinical stage, 80 cases/80 cores, replacing BN02014
Description: Esophagus cancer tissue array, including pathology grade, TNM and clinical stage, 16 cases/78 cores, replacing BC02111
Tissue, Array, Human Tumor, Same Types of Tumor, Esophagus Tumor, esophagus tumors x3, normal control x1, normal placenta (matched with mRNA blots) (Paraffin)
Tissue, Array, Human Tumor, Same Types of Tumor, Esophagus Tumor, esophagus tumors x3, normal control x1, normal placenta (matched with mRNA blots) (Paraffin)
Description: Esophagus cancer and esophagus tissue array, with metastatic cancer, including pathology grade, TNM and clinical satge, 64 cases/192 cores, replacing ES208
Description: Esophagus carcer test tissue array, with normal esophagus tissue as control, including TNM, clinical stage and pathology grade, 2 serial sections, 6 cases/24 cores
Description: Our tissue products are produced by strictly following the IRB ethical standards and procedures and from highest quality tissues. Immediately after collection the tissues are placed in liquid nitrogen and examined by certified pathologists. The thickness of each individual section is ~5um. They are Hematoxylin and Eosin stained and quality tested by immunostaining with anti-beta-actin antibodies. Our tissue products are suitable for various studies on cellular level (RNA localization, Protein expression, etc.) on both normal and pathological cases. It is also an excellent control and educational tool.
Tissue, Array, Human Tumor, Different Types of Tumor, Multi, tissue IV (5), bladder, control, esophagus, control, normal placenta (matched with mRNA blots) (Paraffin)
Tissue, Array, Human Tumor, Different Types of Tumor, Multi, tissue IV (5), bladder, control, esophagus, control, normal placenta (matched with mRNA blots) (Paraffin)
Description: Esophagus cancer with adjacent normal esophagus tissue array, including pathology grade, TNM and clinical stage, 72 cases/72 cores, replacing BC02012
Human Esophagus Tissue Preparation Buffer 1: Normal Esophageal Epithelial Cells
Description: Esophagus adenocarcinoma and normal tissue array, including TNM, clinical stage and pathology grade, 40 cases/80 cores (1.5mm), replacing ES8011a
Human Esophagus Tissue Preparation Buffer 2: Normal Esophageal Smooth Muscle Cells
Description: Esophagus cancer with matched cancer adjacent esophagus tissue array, including pathology grade, TNM and clinical stage (AJCC 8.0), 51 cases/102 cores (1.5 mm).
Description: Esophagus squamous cell carcinoma with normal adjacent esophagus tissue array, including pathology grade and TNM/Stage, 45 cases/90 cores (core size 1.5mm), replacing ES902
Tissue, Array, Human Tumor, Different Types of Tumor, Multi, tissue IV (8), gallbladder, control, esophagus, control, stomach, control, lung, control (matched with Total RNA Northern Blot) (Paraffin)
Tissue, Array, Human Tumor, Different Types of Tumor, Multi, tissue IV (8), gallbladder, control, esophagus, control, stomach, control, lung, control (matched with Total RNA Northern Blot) (Paraffin)
Tissue, Array, Human Tumor, Different Types of Tumor, Multi, tissue II (8), esophagus, control, stomach, control, colon, control, rectum, control (matched with Total RNA Northern Blot) (Paraffin)
Tissue, Array, Human Tumor, Different Types of Tumor, Multi, tissue II (8), esophagus, control, stomach, control, colon, control, rectum, control (matched with Total RNA Northern Blot) (Paraffin)
Description: Esophagus squamous cell carcinoma with matched cancer adjacent tissue and esophagus lymph node tissue array, including pathology grade, TNM and clinical stage, 50 cases/150 cores (core size 1.5mm), replacing ES1505
Tissue, Array, Human Tumor, Different Types of Tumor, Multi, tissue V (8), small intestine, control, esophagus, control, thymoma, control, lung, control (matched with Total RNA Northern Blot) (Paraffin)
Tissue, Array, Human Tumor, Different Types of Tumor, Multi, tissue V (8), small intestine, control, esophagus, control, thymoma, control, lung, control (matched with Total RNA Northern Blot) (Paraffin)
Description: Advanced stage multiple esophagus cancer and normal tissue array, including pathology grade, TNM and clinical stage (AJCC 8.0), 93 cases/93 cores
Esophagus cancer with matched lymph node metastasis tissue array
Description: Multiple esophagus cancer test tissue array with matched or unmatched normal adjacent tissue, 11 cases/24 cores
Tissue, Array, Human Disease (Adult), Digestive System Tumor, Appendix, Colon, Esophagus, Gall Bladder, Liver, Pancreas, Small Intestine, Stomach (Paraffin)
Tissue, Array, Human Disease (Adult), Digestive System Tumor, Appendix, Colon, Esophagus, Gall Bladder, Liver, Pancreas, Small Intestine, Stomach (Paraffin)
Description: Colon tumor test tissue array, with normal colon tissue as control, including TNM, clinical stage and pathology grade, 2 serial sections, 6 cases/12 cores, replaced by T053c
Description: Bone tumor and cartilage tumor tissue array, with normal bone and cartilage tissues, including TNM and clinical stage, 6 cases/24 cores, replacing T261a
Tissue, Genomic DNA, Human Tumor, Esophagus Tumor, BioGenomics
Description: Prostate tumor test tissue array, with normal prostate tissue as control, including TNM and pathology grade, 2 serial sections, 6 cases/24 cores,replaced by T193b