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Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome.

Jönsson JM, Bartuma K, Dominguez-Valentin M, Harbst K, Ketabi Z, Malander S, Jönsson M, Carneiro A, Måsbäck A, Jönsson G, Nilbert M - Fam. Cancer (2014)

Bottom Line: The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction.When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes.Furthermore, separate clustering was achieved in an independent, publically available data set.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology, Department of Clinical Sciences, Skane University Hospital, Lund University, 221 85, Lund, Sweden, jenny-maria.jonsson@med.lu.se.

ABSTRACT
Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics.

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Related in: MedlinePlus

SAM analysis of differentially expressed genes (n = 349) in Lynch syndrome-associated and sporadic ovarian cancers at FDR < 0.01. Clustering was done using the TmeV application with the Pearson correlation distance metric for complete linkage
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Fig1: SAM analysis of differentially expressed genes (n = 349) in Lynch syndrome-associated and sporadic ovarian cancers at FDR < 0.01. Clustering was done using the TmeV application with the Pearson correlation distance metric for complete linkage

Mentions: Unsupervised and supervised hierarchical cluster analysis in the matched dataset of 24 Lynch syndrome-associated and 24 sporadic tumors identified two major clusters related to hereditary status (online resource 2 and Fig. 1, respectively). SAM analysis identified 349 genes that were significantly deregulated between the Lynch syndrome tumors and the sporadic ovarian tumors (FDR < 0.01) (online resource 3). The top up-regulated genes in Lynch syndrome-associated tumors included e.g. PTPRH, BIRC3, SHH and TNFRSF6B. Enriched gene ontology processes were related to cellular growth and proliferation, cell death, and cell-to-cell signaling and interaction (Table 2). In sporadic ovarian cancers, SAM analysis identified up-regulation of e.g. SHC1, which is involved in protein tyrosine kinase activity, and FSCN1, which is related to protein binding (online resource 3).Fig. 1


Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome.

Jönsson JM, Bartuma K, Dominguez-Valentin M, Harbst K, Ketabi Z, Malander S, Jönsson M, Carneiro A, Måsbäck A, Jönsson G, Nilbert M - Fam. Cancer (2014)

SAM analysis of differentially expressed genes (n = 349) in Lynch syndrome-associated and sporadic ovarian cancers at FDR < 0.01. Clustering was done using the TmeV application with the Pearson correlation distance metric for complete linkage
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4231285&req=5

Fig1: SAM analysis of differentially expressed genes (n = 349) in Lynch syndrome-associated and sporadic ovarian cancers at FDR < 0.01. Clustering was done using the TmeV application with the Pearson correlation distance metric for complete linkage
Mentions: Unsupervised and supervised hierarchical cluster analysis in the matched dataset of 24 Lynch syndrome-associated and 24 sporadic tumors identified two major clusters related to hereditary status (online resource 2 and Fig. 1, respectively). SAM analysis identified 349 genes that were significantly deregulated between the Lynch syndrome tumors and the sporadic ovarian tumors (FDR < 0.01) (online resource 3). The top up-regulated genes in Lynch syndrome-associated tumors included e.g. PTPRH, BIRC3, SHH and TNFRSF6B. Enriched gene ontology processes were related to cellular growth and proliferation, cell death, and cell-to-cell signaling and interaction (Table 2). In sporadic ovarian cancers, SAM analysis identified up-regulation of e.g. SHC1, which is involved in protein tyrosine kinase activity, and FSCN1, which is related to protein binding (online resource 3).Fig. 1

Bottom Line: The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction.When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes.Furthermore, separate clustering was achieved in an independent, publically available data set.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology, Department of Clinical Sciences, Skane University Hospital, Lund University, 221 85, Lund, Sweden, jenny-maria.jonsson@med.lu.se.

ABSTRACT
Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics.

Show MeSH
Related in: MedlinePlus