scholarly journals Possible Human Papillomavirus 38 Contamination of Endometrial Cancer RNA Sequencing Samples in The Cancer Genome Atlas Database

2015 ◽  
Vol 89 (17) ◽  
pp. 8967-8973 ◽  
Author(s):  
Majid Kazemian ◽  
Min Ren ◽  
Jian-Xin Lin ◽  
Wei Liao ◽  
Rosanne Spolski ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Human Papillomavirus ◽  
Rna Sequencing ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Cross Contamination ◽  
Rna Seq ◽  
Cancer Genome Atlas ◽  
Genome Atlas

ABSTRACTViruses are causally associated with a number of human malignancies. In this study, we sought to identify new virus-cancer associations by searching RNA sequencing data sets from >2,000 patients, encompassing 21 cancers from The Cancer Genome Atlas (TCGA), for the presence of viral sequences. In agreement with previous studies, we found human papillomavirus 16 (HPV16) and HPV18 in oropharyngeal cancer and hepatitis B and C viruses in liver cancer. Unexpectedly, however, we found HPV38, a cutaneous form of HPV associated with skin cancer, in 32 of 168 samples from endometrial cancer. In 12 of the HPV38-positive (HPV38+) samples, we observed at least one paired read that mapped to both human and HPV38 genomes, indicative of viral integration into the host DNA, something not previously demonstrated for HPV38. The expression levels of HPV38 transcripts were relatively low, and all 32 HPV38+samples belonged to the same experimental batch of 40 samples, whereas none of the other 128 endometrial carcinoma samples were HPV38+, raising doubts about the significance of the HPV38 association. Moreover, the HPV38+samples contained the same 10 novel single nucleotide variations (SNVs), leading us to hypothesize that one patient was infected with this new isolate of HPV38, which was integrated into his/her genome and may have cross-contaminated other TCGA samples within batch 228. Based on our analysis, we propose guidelines to examine the batch effect, virus expression level, and SNVs as part of next-generation sequencing (NGS) data analysis for evaluating the significance of viral/pathogen sequences in clinical samples.IMPORTANCEHigh-throughput RNA sequencing (RNA-Seq), followed by computational analysis, has vastly accelerated the identification of viral and other pathogenic sequences in clinical samples, but cross-contamination during the processing of the samples remain a major problem that can lead to erroneous conclusions. We found HPV38 sequences specifically present in RNA-Seq samples from endometrial cancer patients from TCGA, a virus not previously associated with this type of cancer. However, multiple lines of evidence suggest possible cross-contamination in these samples, which were processed together in the same batch. Despite this potential cross-contamination, our data indicate that we have detected a new isolate of HPV38 that appears to be integrated into the human genome. We also provide general guidelines for computational detection and interpretation of pathogen-disease associations.

scholarly journals PR/SET Domain Family and Cancer: Novel Insights from the Cancer Genome Atlas

2018 ◽  
Vol 19 (10) ◽  
pp. 3250 ◽  
Author(s):  
Anna Sorrentino ◽  
Antonio Federico ◽  
Monica Rienzo ◽  
Patrizia Gazzerro ◽  
Maurizio Bifulco ◽  
...  
Keyword(s):  
Family Members ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Driver Gene ◽  
Rna Seq ◽  
Set Domain ◽  
Primary Tumors ◽  
Cancer Genome Atlas ◽  
Pan Cancer ◽  
Genome Atlas

The PR/SET domain gene family (PRDM) encodes 19 different transcription factors that share a subtype of the SET domain [Su(var)3-9, enhancer-of-zeste and trithorax] known as the PRDF1-RIZ (PR) homology domain. This domain, with its potential methyltransferase activity, is followed by a variable number of zinc-finger motifs, which likely mediate protein–protein, protein–RNA, or protein–DNA interactions. Intriguingly, almost all PRDM family members express different isoforms, which likely play opposite roles in oncogenesis. Remarkably, several studies have described alterations in most of the family members in malignancies. Here, to obtain a pan-cancer overview of the genomic and transcriptomic alterations of PRDM genes, we reanalyzed the Exome- and RNA-Seq public datasets available at The Cancer Genome Atlas portal. Overall, PRDM2, PRDM3/MECOM, PRDM9, PRDM16 and ZFPM2/FOG2 were the most mutated genes with pan-cancer frequencies of protein-affecting mutations higher than 1%. Moreover, we observed heterogeneity in the mutation frequencies of these genes across tumors, with cancer types also reaching a value of about 20% of mutated samples for a specific PRDM gene. Of note, ZFPM1/FOG1 mutations occurred in 50% of adrenocortical carcinoma patients and were localized in a hotspot region. These findings, together with OncodriveCLUST results, suggest it could be putatively considered a cancer driver gene in this malignancy. Finally, transcriptome analysis from RNA-Seq data of paired samples revealed that transcription of PRDMs was significantly altered in several tumors. Specifically, PRDM12 and PRDM13 were largely overexpressed in many cancers whereas PRDM16 and ZFPM2/FOG2 were often downregulated. Some of these findings were also confirmed by real-time-PCR on primary tumors.

scholarly journals Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas

Oncotarget ◽  
2018 ◽  
Vol 9 (24) ◽  
pp. 17093-17103 ◽  
Author(s):  
David S. Guttery ◽  
Kevin Blighe ◽  
Konstantinos Polymeros ◽  
R. Paul Symonds ◽  
Salvador Macip ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Racial Differences ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

scholarly journals Μελέτη μοριακών σηματοδοτικών μηχανισμών επαγωγής της κυτταρικής επιβίωσης και αποδιαφοροποίησης στον καρκίνο

2019 ◽  
Author(s):  
Ευστάθιος-Ιάσων Βλαχάβας
Keyword(s):  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Rna Seq ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Ο όρος καρκίνος χρησιμοποιείται όχι για μια ασθένεια, αλλά για ένα ευρύτερο σύνολο συσχετιζόμενων νοσημάτων, οι οποίες περιγράφονται από ένα κοινό χαρακτηριστικό: την αφύσικη ανάπτυξη κυττάρων που διαιρούνται ανεξέλεγκτα και μπορούν να διηθήσουν παρακείμενους ιστούς. Η μελέτη των μοριακών μηχανισμών που εμπλέκονται στη παθοφυσιολογία των καρκίνου, αποτελεί πεδίο έντονης έρευνας, γιατί η κατανόησή τους συνδέεται άμεσα με την ορθή αντιμετώπιση της νόσου. Στην παρούσα διατριβή, εστιάζουμε στον καρκίνο του παχέος εντέρου. Η πλειοψηφία των όγκων του παχέος εντέρου είναι αδενοκαρκινώματα, τα οποία προκύπτουν από τη δημιουργία πολυπόδων που σχηματίζονται στο εσωτερικό τοίχωμα του παχέος εντέρου και μπορούν να εξελιχθούν σε νεοπλασίες. Ο καρκίνος του παχέος εντέρου είναι μια ιδιαίτερα σύνθετη ασθένεια, με έντονα μεταβλητά μοριακά και γενετικά χαρακτηριστικά και με διαφορική απόκριση σε φαρμακευτικά σχήματα. Περίπου το 40% των περιπτώσεων ανιχνεύονται σε πρώιμο στάδιο με το ποσοστό της πενταετούς επιβίωσης να κυμαίνεται στο 90%. Επιπρόσθετα, αποτελεί μια αιτία θνησιμότητας στις χώρες του ανεπτυγμένου κόσμου, κυρίως λόγω του υψηλού μεταστατικού δυναμικού που παρουσιάζει. Συνολικά, τα παραπάνω στοιχεία καθιστούν επιτακτική την αξιοποίηση όλων των διαθέσιμων μοριακών πληροφοριών αλλά και ιατροβιολογικών δεδομένων για την εφαρμογή εξατομικευμένης θεραπείας στα πλαίσια της μεταφραστικής έρευνας.Την τελευταία δεκαετία, η εκτεταμένη αξιοποίηση των τεχνικών υψηλής απόδοσης, όπως οι μικροσυστοιχίες γονιδίων και οι τεχνολογίες αλληλούχισης νέας γενιάς για την ανάλυση της γονιδιακής έκφρασης σε διάφορους τύπους καρκίνου του παχέος εντέρου, συνέβαλε σημαντικά στην ταυτοποίηση σημαντικών γονιδιακών μεταλλαγών και στον χαρακτηρισμό γονιδίων που εμπλέκονται στην παθοφυσιολογία του συγκεκριμένου καρκίνου. Αν και οι τεχνολογίες αλληλούχισης νέας γενιάς παρουσιάζουν σημαντικές τεχνολογικές βελτιώσεις, οι μικροσυστοιχίες DNA εξακολουθούν να παραμένουν δημοφιλείς για την ανάλυση του μεταγραφώματος, αφενός γιατί παραμένουν πιο οικονομικές και αφετέρου προϋποθέτουν μια λιγότερο σύνθετη προετοιμασία δειγμάτων, συγκριτικά με τις μεθοδολογίες αλληλούχισης. Αντιπροσωπευτικά παραδείγματα για τη συμβολή των τεχνολογιών υψηλής απόδοσης αποτελούν ερευνητικές δημοσιεύσεις από τη διεθνή ερευνητική συνεργασία (The Cancer Genome Atlas) για τον μοριακό χαρακτηρισμού του καρκίνου του παχέος εντέρου, καθώς και τον χαρακτηρισμό συγκεκριμένων μοριακών υποτύπων με βάση γονιδιωματικά δεδομένα από διαφορετικές ερευνητικές ομάδες. Ωστόσο, η ιδιαίτερη ετερογένεια που παρουσιάζει ο συγκεκριμένος καρκίνος αλλά και η δυσκολία της ερμηνείας μοριακών δεδομένων υψηλής διαστασιμότητας που προκύπτουν από την ανάλυση μικροσυστοιχιών αλλά και DNA/RNA-Seq τεχνολογιών, δυσχεραίνουν την αξιοποίηση των διαφόρων γονιδιακών υπογραφών που περιγράφουν ένα συγκεκριμένο καρκινικό φαινότυπο, στην κλινική εφαρμογή.

scholarly journals Potential prognostic impact of EBV RNA‐seq reads in gastric cancer: a reanalysis of The Cancer Genome Atlas cohort

FEBS Open Bio ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 455-467 ◽  
Author(s):  
Daichi Sadato ◽  
Mina Ogawa ◽  
Chizuko Hirama ◽  
Tsunekazu Hishima ◽  
Shin‐Ichiro Horiguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Prognostic Impact ◽  
Rna Seq ◽  
Cancer Genome Atlas ◽  
Genome Atlas

scholarly journals Biological Validation of RNA Sequencing Data From Formalin-Fixed Paraffin-Embedded Primary Melanomas

2018 ◽  
pp. 1-19 ◽  
Author(s):  
Lawrence N. Kwong ◽  
Mariana Petaccia De Macedo ◽  
Lauren Haydu ◽  
Aron Y. Joon ◽  
Michael T. Tetzlaff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Formalin Fixed Paraffin ◽  
Ffpe Samples ◽  
Formalin Fixed Paraffin Embedded ◽  
Cancer Genome Atlas ◽  
Formalin Fixed ◽  
Genome Atlas

Purpose Initiatives such as The Cancer Genome Atlas and International Cancer Genome Consortium have generated high-quality, multiplatform molecular data from thousands of frozen tumor samples. Although these initiatives have provided invaluable insight into cancer biology, a tremendous potential resource remains largely untapped in formalin-fixed, paraffin-embedded (FFPE) samples that are more readily available but which can present technical challenges because of crosslinking of fragile molecules such as RNA. Materials and Methods We extracted RNA from FFPE primary melanomas and assessed two gene expression platforms—genome-wide RNA sequencing and targeted NanoString—for their ability to generate coherent biologic signals. To do so, we generated an improved approach to quantifying gene expression pathways. We refined pathway scores through correlation-guided gene subsetting. We also make comparisons to The Cancer Genome Atlas and other publicly available melanoma datasets. Results The comparison of the gene expression patterns to each other, to established biologic modules, and to clinical and immunohistochemical data confirmed the fidelity of biologic signals from both platforms using FFPE samples to known biology. Moreover, correlations with patient outcome data were consistent with previous frozen-tissue–based studies. Conclusion FFPE samples from previously difficult-to-access cancer types, such as small primary melanomas, represent a valuable and previously unexploited source of analyte for RNA sequencing and NanoString platforms. This work provides an important step toward the use of such platforms to unlock novel molecular underpinnings and inform future biologically driven clinical decisions.

scholarly journals DNA Methylation–Based Classifier for Accurate Molecular Diagnosis of Bone Sarcomas

2017 ◽  
pp. 1-11 ◽  
Author(s):  
S. Peter Wu ◽  
Benjamin T. Cooper ◽  
Fang Bu ◽  
Christopher J. Bowman ◽  
J. Keith Killian ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Synovial Sarcoma ◽  
Ewing Sarcoma ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Cpg Sites ◽  
A Genome ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Purpose Pediatric sarcomas provide a unique diagnostic challenge. There is considerable morphologic overlap between entities, increasing the importance of molecular studies in the diagnosis, treatment, and identification of therapeutic targets. We developed and validated a genome-wide DNA methylation–based classifier to differentiate between osteosarcoma, Ewing sarcoma, and synovial sarcoma. Methods DNA methylation status of 482,421 CpG sites in 10 Ewing sarcoma, 11 synovial sarcoma, and 15 osteosarcoma samples were determined using the Illumina Infinium HumanMethylation450 array. We developed a random forest classifier trained from the 400 most differentially methylated CpG sites within the training set of 36 sarcoma samples. This classifier was validated on data drawn from The Cancer Genome Atlas synovial sarcoma, TARGET-Osteosarcoma, and a recently published series of Ewing sarcoma. Results Methylation profiling revealed three distinct patterns, each enriched with a single sarcoma subtype. Within the validation cohorts, all samples from The Cancer Genome Atlas were accurately classified as synovial sarcoma (10 of 10; sensitivity and specificity, 100%), all but one sample from TARGET-Osteosarcoma were classified as osteosarcoma (85 of 86; sensitivity, 98%; specificity, 100%), and 14 of 15 Ewing sarcoma samples were classified correctly (sensitivity, 93%; specificity, 100%). The single misclassified osteosarcoma sample demonstrated high EWSR1 and ETV1 expression on RNA sequencing, although no fusion was found on manual curation of the transcript sequence. Two additional clinical samples that were difficult to classify by morphology and molecular methods were classified as osteosarcoma; one had been suspected of being a synovial sarcoma and the other of being Ewing sarcoma on initial diagnosis. Conclusion Osteosarcoma, synovial sarcoma, and Ewing sarcoma have distinct epigenetic profiles. Our validated methylation-based classifier can be used to provide diagnostic assistance when histologic and standard techniques are inconclusive.

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