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Genomic analysis of tumors is transforming our understanding of cancer. However, although a great deal of attention is paid to the accuracy of the cancer genomic data itself, less attention has been paid to the accuracy of the associated clinical information that renders the genomic data useful for research. In this brief communication, we suggest that omissions and errors in clinical annotations have a major impact on the interpretation of cancer genomic data. We describe our discovery of annotation omissions and errors when reviewing an already carefully annotated colorectal cancer gene expression dataset from our laboratory. The potential importance of clinical annotation omissions and errors was then explored using simulation analyses with an independent genomic dataset. We suggest that the completeness and veracity of clinical annotations accompanying cancer genomic data require renewed focus by the oncology research community, when planning new collections and when interpreting existing cancer genomic data.

Background: Different aspects of coronavirus disease 2019 (COVID-19) in children have not been well understood so far Objectives: In this paper, we reported the clinical, Paraclinical, and epidemiological features of the hospitalized children infected with COVID-19 in the southeast of Iran Methods: This cross-sectional study was conducted in six hospitals affiliated to Kerman University of Medical Sciences All children who were under the age of 15 years old hospitalized with acute respiratory infection from February 20 to May 14, 2020, were included in this study Demographic characteristics, past medical history data, and disease-related data such as symptoms, signs, radiologic, and laboratory data were collected Results: Of 97 hospitalized children with an acute respiratory infection, 13 cases (13 4%) had been diagnosed to be infected by COVID-19 The mean (standard deviation) and median of age of the patients with COVID-19 were 68 0 (55 9) and 60 months, respectively Fever (n = 11, 84 6%), cough (n = 8, 61 5%), respiratory distress (n = 5, 38 5%), and gastrointestinal symptoms (n = 5, 38 5%) were known as the most common symptoms in patients with COVID-19 Frequency fever (84 6% vs 47 6%, P = 0 016) and respiratory distress (38 8% vs 13 1%, P = 0 022) were significantly higher in patients with COVID-19 compared to non-COVID individuals Frequency of admission in the intensive care unit (38 5% vs 27 4%, P = 0 668) and death rate (15 4% vs 7 1%, P = 0 291) were higher in patients with COVID-19 compared to non-COVID-19 subjects, but there were no significant differences between the two groups in term of these variables Conclusions: A low proportion of children hospitalized with acute respiratory syndrome were infected by COVID-19 Most of the children with COVID-19 recovered with supportive care with no need for any specific treatment © 2020, Author(s)

Diffuse gastric cancer (DGC) is one of the two primary types of stomach cancer. Carriers of germline mutations in the gene encoding E-cadherin are predisposed to DGC. The primary aim of the present study was to determine if genomic instability is an early event in DGC and how it may lead to disease progression. Chromosomal aberrations in early intramucosal hereditary diffuse gastric cancer (eHDGC) were assessed using array comparative genomic hybridization (array CGH). Notably, no aneuploidy or other large-scale chromosomal rearrangements were detected. Instead, all aberrations affected small regions (< 4.8 Mb) and were predominantly deletions. Analysis of DNA sequence patterns revealed that essentially all aberrations possessed the characteristics of common fragile sites. These results and the results of subsequent immunohistochemical examinations demonstrated that unlike advanced DGC, eHDGCs is characterized by low levels of genomic instability at fragile sites. Furthermore, they express an active DNA damage response, providing a molecular basis for the observed indolence of eHDGC. This finding is an important step to understanding the pathology underlying natural history of DGC and supports a revision of the current definition of eHDGC as a malignant disease.

Compromised quality of formalin-fixed paraffin-embedded (FFPE)-derived DNA has compounded the use of archival specimens for array-based genomic studies. Recent technological advances have led to first successes in this field; however, there is currently no general agreement on the most suitable platform for the array-based analysis of FFPE DNA. In this study, FFPE and matched fresh-frozen (FF) specimens were separately analyzed with Affymetrix single nucleotide polymorphism (SNP) 6.0 and Agilent 4x44 K oligonucleotide arrays to compare the genomic profiles from the two tissue sources and to assess the relative performance of the two platforms on FFPE material. Genomic DNA was extracted from matched FFPE–FF pairs of normal intestinal epithelium from four patients and were applied to the SNP and oligonucleotide platforms according to the manufacturer-recommended protocols. On the Affymetrix platform, a substantial increase in apparent copy number alterations was observed in all FFPE tissues relative to their matched FF counterparts. In contrast, FFPE and matched FF genomic profiles obtained via the Agilent platform were very similar. Both the SNP and the oligonucleotide platform performed comparably on FF material. This study demonstrates that Agilent oligonucleotide array comparative genomic hybridization generates reliable results from FFPE extracted DNA, whereas the Affymetrix SNP-based array seems less suitable for the analysis of FFPE material.

The association between cell proliferation and the malignant potential of colon cancer is not well understood. Here, we evaluated this association using a colon-specific gene proliferation signature (GPS). The GPS was derived by combining gene expression data obtained from the analysis of a cancer cell line model and a published colon crypt profile. The GPS was overexpressed in both actively cycling cells in vitro and the proliferate compartment of colon crypts. K-means clustering was used to independantly stratify two cohorts of colon tumours into two groups with high and low GPS expression. Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (P

Introduction Mounting molecular evidence suggests that invasive lobular carcinoma (ILC) is developing from in situ lesions, atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS). However, little is known about the mechanisms promoting the progression of lobular breast cancer (LBC) to invasive disease. Here, we investigated whether c-Src kinase, an established inducer of invasive states, contributes to the progression from ALH/LCIS to ILC. Methods Immunochemistry for c-Src and other cancer-related molecules was performed on archived tissue specimens from 57 LBC patients. Relative c-Src activity was estimated by comparing fluorescence intensity of ILC with that of adjacent ALH/LCIS and nonneoplastic epithelia after staining with an antibody against active c-Src. Expression of active c-Src was correlated with markers of invasion and malignancy and with relapse among LBC patients. Results Levels of activated c-Src were increased in ILC relative to ALH/LCIS (1.63-fold ± 0.24 SD) and nonneoplastic epithelia (1.47 ± 0.18 SD). Increased c-Src levels correlated with the activation of c-Src downstream targets (Fak, Stat-3) and the expression of mesenchymal markers. ILC cells with activated c-Src co-expressed metastatic markers (Opn, Cxcr4) and included cells positive for the cancer stem cell marker Aldh1. A tendency for high c-Src levels (P = 0.072) was observed among the seven LBC patients with relapsed disease. Conclusions Our data indicate elevated c-Src activity in ILC relative to noninvasive neoplastic tissue. The associated molecular changes suggest that c-Src promotes LBC invasiveness by inducing an epithelial-mesenchymal transition. Therefore, c-Src antagonists might counteract the acquisition of invasiveness during LBC progression. Inhibition of c-Src may also affect ILC cells thought to have a high metastatic potential and to be capable of initiating/maintaining tumor growth. Together with the possible association between high c-Src levels and disease recurrence, our findings encourage the evaluation of c-Src antagonists for the treatment of LBC.

Tumour cells have to undergo gene expression changes in order to metastasise and adapt to a new site. We investigated these changes in liver metastases of colorectal cancer by using genome-wide microarray analysis to profile the expression of 48 primary tumours and 28 liver metastases. Statistical analysis of these expression profiles using the significance analysis of microarrays (SAM) method identified 778 genes differentially expressed between primary tumours and metastases. Gene ontology analysis revealed that genes associated with tissue remodelling and immune response were upregulated in metastases relative to primary tumours, whereas genes associated with proliferation and oxidative phosphorylation were downregulated. Quantitative real-time PCR confirmed the differential expression of selected genes, osteopontin, versican, ADAM17, CKS2, PRDX1, CXCR4, CXCL12, and LCN2. The upregulation of genes associated with tissue remodelling and immune response are likely to be involved in metastatic invasion and colonisation of the new site because these genes can promote tumour progression. However, downregulation of genes associated with proliferation suggests that proliferation in metastases was reduced relative to primary tumours.

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide - over half of those diagnosed will die from the disease. An important role for the immune response in controlling CRC has been demonstrated in numerous animal models and in human patients. The extent of T cell infiltration in the primary tumour is a better predictor of survival in CRC patients than traditional staging. Further, recent data by our lab and others have shown a correlation between immune response gene expression and favourable patient outcome. Despite the presence of an immune response, tumours still develop and grow. We hypothesised that the T cell response in the lymph nodes, i.e. the site of immune response initiation, may be a better predictor of patient outcome than that of the primary tumour. To this end, we analysed T cell subsets in the lymph nodes of Dukes' Stage B colorectal cancer (non metastatic) in a cohort of patients from New Zealand who had clinical follow-up. We found that, as is true for CD8+ T cells infiltrating the primary tumour, the number of CD8+ T cells on the lymph nodes correlated with a favourable patient outcome. However, the number of total CD4+ T cells in the lymph node was not correlated with patient outcome. The subtypes of CD4+ and CD8+ T cells, e.g. regulatory, effector, memory, are yet to be investigated. However, our data shows that the anti-tumour immune response appears to be initiated effectively in the lymph node and implies that the tumour environment may act directly to down-modulate an effective immune response.