Breast tumors from CHEK2 1100delC mutation carriers: genomic landscape and clinical implications
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Taru Muranen
PROVIDER: E-GEOD-24707 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Breast tumors from CHEK2 1100delC-mutation carriers: genomic landscape and clinical implications.
Muranen Taru A TA Greco Dario D Fagerholm Rainer R Kilpivaara Outi O Kämpjärvi Kati K Aittomäki Kristiina K Blomqvist Carl C Heikkilä Päivi P Borg Ake A Nevanlinna Heli H
Breast cancer research : BCR 20110920 5
<h4>Introduction</h4>Checkpoint kinase 2 (CHEK2) is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about twofold. We investigated gene copy-number aberrations and gene-expression profiles that are typical for breast tumors of CHEK2 1100delC-mutation carriers.<h4>Methods</h4>In total, 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array-comparative genomic hybridization (aCGH) and g ...[more]
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Project description:Abstract Introduction: CHEK2 is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about two fold. We pursued to investigate gene copy number aberrations and gene expression profiles that are typical for breast tumors of CHEK2 1100delC mutation carriers. Materials and methods: A total of 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array comparative genomic hybridization (aCGH) and gene expression experiments (GEX). After dimensionality reduction with CGHregions R package, CHEK2 1100delC associated regions in the aCGH data were detected by Wilcoxon rank sum test. Linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by Bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2 and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3 and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors nominating them as candidates for CHEK2 1100delC associated tumor progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM and LRP1 on 12q13. Altogether 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44 lowered expression levels. Our results suggest WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions we have identified potential drivers of CHEK2 1100delC associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of CHEK2 1100delC mutation. 79 samples from breast tumors: 22 tumors from CHEK2 1100delC mutation carriers, 57 other tumors Five files attached represent segmented values, copy number calls, gain, loss and normal copy number probabilities.
2011-05-10 | E-GEOD-24698 | biostudies-arrayexpress
Project description:Introduction: CHEK2 is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about two fold. We pursued to investigate gene copy number aberrations and gene expression profiles that are typical for breast tumors of CHEK2 1100delC mutation carriers. Materials and methods: A total of 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array comparative genomic hybridization (aCGH) and gene expression experiments (GEX). After dimensionality reduction with CGHregions R package, CHEK2 1100delC associated regions in the aCGH data were detected by Wilcoxon rank sum test. Linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by Bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2 and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3 and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors nominating them as candidates for CHEK2 1100delC associated tumor progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM and LRP1 on 12q13. Altogether 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44 lowered expression levels. Our results suggest WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions we have identified potential drivers of CHEK2 1100delC associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of CHEK2 1100delC mutation. 78 samples from breast tumors: 13 tumors from CHEK2 1100delC mutation carriers, 65 other tumors
2011-05-10 | E-GEOD-24697 | biostudies-arrayexpress
Project description:Breast tumors from CHEK2 1100delC mutation carriers: genomic landscape and clinical implications (GEX)
| PRJNA133633 | ENA
Project description:Introduction: CHEK2 is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about two fold. We pursued to investigate gene copy number aberrations and gene expression profiles that are typical for breast tumors of CHEK2 1100delC mutation carriers. Materials and methods: A total of 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array comparative genomic hybridization (aCGH) and gene expression experiments (GEX). After dimensionality reduction with CGHregions R package, CHEK2 1100delC associated regions in the aCGH data were detected by Wilcoxon rank sum test. Linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by Bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2 and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3 and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors nominating them as candidates for CHEK2 1100delC associated tumor progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM and LRP1 on 12q13. Altogether 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44 lowered expression levels. Our results suggest WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions we have identified potential drivers of CHEK2 1100delC associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of CHEK2 1100delC mutation.
2011-05-10 | GSE24698 | GEO
Project description:Introduction: CHEK2 is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about two fold. We pursued to investigate gene copy number aberrations and gene expression profiles that are typical for breast tumors of CHEK2 1100delC mutation carriers. Materials and methods: A total of 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array comparative genomic hybridization (aCGH) and gene expression experiments (GEX). After dimensionality reduction with CGHregions R package, CHEK2 1100delC associated regions in the aCGH data were detected by Wilcoxon rank sum test. Linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by Bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2 and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3 and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors nominating them as candidates for CHEK2 1100delC associated tumor progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM and LRP1 on 12q13. Altogether 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44 lowered expression levels. Our results suggest WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions we have identified potential drivers of CHEK2 1100delC associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of CHEK2 1100delC mutation.
2011-05-10 | GSE24697 | GEO
Project description:Breast tumors from CHEK2 1100delC mutation carriers: genomic landscape and clinical implications (CGH)
| PRJNA133635 | ENA
Project description:Clinically evident oral lesions, oral epithelial dysplasia, precede development of oral squamous cell carcinomas (SCC) and are considered to transform to cancer by acquisition of genetic or epigenetic alterations. Here, we show that, +3q24-qter, -8pter-p23.1, +8q12-q24.2 and +20 are early events identifying two pathways to oral cancers that differ in clinical behavior. One or more of these copy number aberrations is present in the major subgroup (3q8pq20 subtype, 75-80% of lesions) that develops with chromosomal instability and risk for metastasis, while they are absent from the smaller and chromosomally stable non-3q8pq20 subgroup (20-25% of lesions) associated with low risk for metastasis. Thus, +3q, -8p, +8q and +20 is a biomarker for oral SCC metastasis. On the other hand, while increased numbers of genomic alterations can be harbingers of progression to cancer, dysplastic lesions lacking copy number changes cannot be considered benign as they are potential precursors to non-3q8pq20 oral SCC. 63 oral SCCs and adjacent regions of normal tissue, 44 oral dysplasias
2011-11-18 | E-GEOD-28407 | biostudies-arrayexpress
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2023-03-29 | E-MTAB-12468 | biostudies-arrayexpress
Project description:The aim of this analysis was to better understand the complex symbiotic stage of Tuber melanosporum by combining the use of laser capture microdissection and microarray gene expression analysis. We isolated the fungal/soil (i.e. the mantle) and the fungal/plant (i.e. the Hartig net) interfaces from transverse sections of T. melanosporum/Corylus avellana ectomycorrhizas and identified the transcriptional landscape associated with each compartment. We compared these data to the transcriptome of ectomycorrhizal root tips, free-living mycelium and fruiting bodies of Tuber melanosporum (Series GSE17529). The T. melanosporum custom-exon expression array (4 x 72K) manufactured by Roche NimbleGen Systems Limited (Madison, WI) contained five independent, nonidentical, 60-mer probes per gene model coding sequence. Included in the oligoarray were 12,232 annotated gene models, 3,913 random 60-mer control probes and labelling controls. Sequences used for the oligonucleotide design were from an early draft of the gene catalog containing several TE families. For 1,876 gene models, technical duplicates were included on the array. We performed 6 hybridizations (NimbleGen) with samples derived from microdissected mantles (3 biological replicates) and Hartig nets ((3 biological replicates each) from T. melanosporum/Corylus avellana ectomycorrhizal root tips . All samples were labeled with Cy3.
2013-03-01 | E-GEOD-36870 | biostudies-arrayexpress