The biology underlying nodal metastasis is poorly understood. Transcriptome profiling has helped to characterize both primary tumors seeding nodal metastasis and the metastasis themselves. The interpretation of these data, however, is not without ambiguities. Here we profiled the transcriptomes of 17 papillary thyroid cancer (PTC) nodal metastases, associated primary tumors and primary tumors from N0 patients. We also included patient-matched normal thyroid and lymph node samples as controls to address some limits of previous studies. We found that the transcriptomes of patient-matched primary tumors and metastases were more similar than of unrelated metastases/primary pairs, a result also reported in other organ systems, and that part of this similarity reflected patient background. We found that the comparison of patient-matched primary tumors and metastases was heavily confounded by the presence of lymphoid tissues in the metastasis samples. An original data adjustment procedure was developed to circumvent this problem. It revealed a differential expression of stroma-related gene expression signatures also regulated in other organ systems. The comparison of N0 vs. N+ primary tumors uncovered a signal irreproducible across independent PTC datasets. This signal was also detectable when comparing the normal thyroid tissues adjacent to N0 and N+ tumors, suggesting a cohort specific bias also likely to be present in previous studies with similar statistical power. Classification of N0 vs. N+ yielded an accuracy of 63%, but additional statistical controls not presented in previous studies, revealed that this is likely to occur by chance alone. To address this issue, we used large datasets from The Cancer Genome Atlas and showed that N0 vs. N+ classification rates could not be reached randomly for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers.
Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer.
Sex
View SamplesMicroarrays have revolutionized breast cancer (BC) research by enabling studies of gene expression on a transcriptome-wide scale. Recently, RNA-Sequencing (RNA-Seq) has emerged as an alternative for precise readouts of the transcriptome. To date, no study has compared the ability of the two technologies to quantify clinically relevant individual genes and microarray-derived gene expression signatures (GES) in a set of BC samples encompassing the known molecular BC's subtypes. To accomplish this, the RNA from 57 BCs representing the four main molecular subtypes (triple negative, HER2 positive, luminal A, luminal B), was profiled with Affymetrix HG-U133 Plus 2.0 chips and sequenced using the Illumina HiSeq 2000 platform. The correlations of three clinically relevant BC genes, six molecular subtype classifiers, and a selection of 21 GES were evaluated.
Transfer of clinically relevant gene expression signatures in breast cancer: from Affymetrix microarray to Illumina RNA-Sequencing technology.
Specimen part, Disease stage
View SamplesEORTC 10994 is a phase III clinical trial comparing FEC with ET in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 100 ng total RNA per chip were amplified using the Affymetrix small sample protocol (IVT then Enzo). 49 tumours were tested on Affymetrix U133A chips. The CEL files were quantile normalised together using rma. Clinical response data are not available yet.
Identification of molecular apocrine breast tumours by microarray analysis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View SamplesSox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in human, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/-catenin dependent manner. Deletion of Sox9 together with the constitutive activation of Hedgehog (HH) signaling completely prevents BCC formation and leads to a progressive loss of oncogene expressing cells. Transcriptional profiling of oncogene expressing cells with Sox9 deletion, combined with in vivo ChIP-sequencing uncovers a cancer-specific gene network regulated by Sox9 that promotes stemness, extracellular matrix (ECM) deposition and cytoskeleton remodeling while repressing epidermal differentiation. Our study identifies the molecular mechanisms regulated by Sox9 that links tumor initiation and invasion.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View SamplesPurpose: A number of microarray studies have reported distinct molecular profiles of breast cancers (BC): basal-like, ErbB2-like and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER)-positive subtypes has been inconsistent. Refinement of their molecular definition is therefore needed.
Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade.
Age, Disease stage
View SamplesBasal cell carcinoma initiating cells undergo profound and rapid reprogramming into embryonic hair follicle progenitor like fate upon SmoM2 expression. Activation of Wnt/-catenin signaling pathways is required in a cell autonomous manner for the reprogramming of adult IFE progenitors into EHFP-like fate as well as for tumor initiation.
Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation.
Specimen part
View SamplesBackground: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profi les of breast cancers and whether such profi les could be used to improve histologic grading.
Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.
Age, Disease stage
View SamplesPurpose: There is growing evidence that interaction between stromal and tumor cells is pivotal in breast cancer progression and response to therapy. Since the pioneer work of Allinen et al. suggested that during breast cancer progression striking changes occur in CD10+ stromal cells, we aimed to better characterize this cell population and its clinical relevance.
Characterization and clinical evaluation of CD10+ stroma cells in the breast cancer microenvironment.
Specimen part, Disease stage
View SamplesBackground: The prognostic value of histologic grade (HG) in invasive lobular carcinoma (ILC) remains uncertain, and most ILC tumors are graded as HG2. Genomic grade (GG) is a 97-gene signature that improves the prognostic value of HG. This study evaluates whether GG may overcome the limitations of HG in ILC.
Genomic grade adds prognostic value in invasive lobular carcinoma.
Sex, Specimen part, Disease, Disease stage
View Samples