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Integrative genomic and transcriptomic characterization of papillary carcinomas of the breast

View Article: PubMed Central - PubMed

ABSTRACT

Papillary carcinoma (PC) is a rare type of breast cancer, which comprises three histologic subtypes: encapsulated PC (EPC), solid PC (SPC) and invasive PC (IPC). Microarray-based gene expression and Affymetrix SNP 6.0 gene copy number profiling, and RNA-sequencing revealed that PCs are luminal breast cancers that display transcriptomic profiles distinct from those of grade- and estrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs), and that the papillary histologic pattern is unlikely to be underpinned by a highly recurrent expressed fusion gene or a highly recurrent expressed mutation. Despite displaying similar patterns of gene copy number alterations, significant differences in the transcriptomic profiles of EPCs, SPCs and IPCs were found, and may account for their different histologic features.

No MeSH data available.


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Ingenuity Pathway Analysis of 780 unique genes expressed at significantly lower levels in 16 papillary carcinomas than in 16 grade- and ER-matched invasive ductal carcinomas of no special type. (A) Genes of the ‘Cellular Growth and Proliferation’ were down-regulated in PCs in comparison with IDCs-NSTs. (B) Cell assembly and organization genes were down-regulated in PCs versus IDC-NSTs. (C) Genes involved in cellular movement and migration were down-regulated in PCs compared with grade- and ER-matched IDC-NSTs. IDC-NST, invasive ductal carcinoma of no special type; PC, papillary carcinoma.
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fig2: Ingenuity Pathway Analysis of 780 unique genes expressed at significantly lower levels in 16 papillary carcinomas than in 16 grade- and ER-matched invasive ductal carcinomas of no special type. (A) Genes of the ‘Cellular Growth and Proliferation’ were down-regulated in PCs in comparison with IDCs-NSTs. (B) Cell assembly and organization genes were down-regulated in PCs versus IDC-NSTs. (C) Genes involved in cellular movement and migration were down-regulated in PCs compared with grade- and ER-matched IDC-NSTs. IDC-NST, invasive ductal carcinoma of no special type; PC, papillary carcinoma.

Mentions: SAM analysis further supported this observation, given that 8.3% of the significantly regulated probes (795 unique genes) were differentially expressed between PCs and histologic grade- and ER-matched IDC-NSTs (FDR <10%), of which 780 unique genes were expressed at significantly lower levels in PCs than in grade- and ER-matched IDC-NSTs (Supplementary Table S5). IPA and DAVID gene ontology and pathway analysis employing these 780 genes revealed a significant enrichment for genes involved in cellular growth and proliferation (e.g. KIT, ALDH1A3, ELF4, CCND2 and MAP4K4, right-tailed Fisher exact test p-value<0.0001, Figure 2A, Supplementary Table S5). This is consistent with the observation that PCs are a form of ER-positive breast cancer with an excellent outcome (Rakha et al., 2011), given that the expression levels of proliferation-related genes have been shown to constitute one of the strongest predictors of outcome of ER-positive breast cancers (Reis-Filho and Pusztai, 2011). Other genes expressed at significantly lower levels in PCs than in grade- and ER-matched IDC-NSTs included those involved in cell assembly and organization (e.g. LAMB1, ACTN1 and collagen genes such as COL1A2, COL6A1, COL8A1, COL12A1, right-tailed Fisher exact test p-value<0.0001, Figure 2B) and cellular movement and migration (e.g. MMP3, MMP7 and THBS4, right-tailed Fisher exact test p-value<0.0001, Figure 2C). Consistent with these observations, DAVID KEGG pathway analysis revealed that the “cell adhesion molecules” (CAMs) pathway was the most significantly enriched for genes expressed at lower levels in PCs than in IDC-NSTs (data not shown). By contrast, 15 genes involved in cellular homeostasis (e.g. QSOX1) and angiogenesis (e.g. VEGFA, ESM1, SLC4A11 and VCAM1) were expressed at significantly higher levels in PCs than in grade- and ER-matched IDC-NSTs (Supplementary Table S5).


Integrative genomic and transcriptomic characterization of papillary carcinomas of the breast
Ingenuity Pathway Analysis of 780 unique genes expressed at significantly lower levels in 16 papillary carcinomas than in 16 grade- and ER-matched invasive ductal carcinomas of no special type. (A) Genes of the ‘Cellular Growth and Proliferation’ were down-regulated in PCs in comparison with IDCs-NSTs. (B) Cell assembly and organization genes were down-regulated in PCs versus IDC-NSTs. (C) Genes involved in cellular movement and migration were down-regulated in PCs compared with grade- and ER-matched IDC-NSTs. IDC-NST, invasive ductal carcinoma of no special type; PC, papillary carcinoma.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037246&req=5

fig2: Ingenuity Pathway Analysis of 780 unique genes expressed at significantly lower levels in 16 papillary carcinomas than in 16 grade- and ER-matched invasive ductal carcinomas of no special type. (A) Genes of the ‘Cellular Growth and Proliferation’ were down-regulated in PCs in comparison with IDCs-NSTs. (B) Cell assembly and organization genes were down-regulated in PCs versus IDC-NSTs. (C) Genes involved in cellular movement and migration were down-regulated in PCs compared with grade- and ER-matched IDC-NSTs. IDC-NST, invasive ductal carcinoma of no special type; PC, papillary carcinoma.
Mentions: SAM analysis further supported this observation, given that 8.3% of the significantly regulated probes (795 unique genes) were differentially expressed between PCs and histologic grade- and ER-matched IDC-NSTs (FDR <10%), of which 780 unique genes were expressed at significantly lower levels in PCs than in grade- and ER-matched IDC-NSTs (Supplementary Table S5). IPA and DAVID gene ontology and pathway analysis employing these 780 genes revealed a significant enrichment for genes involved in cellular growth and proliferation (e.g. KIT, ALDH1A3, ELF4, CCND2 and MAP4K4, right-tailed Fisher exact test p-value<0.0001, Figure 2A, Supplementary Table S5). This is consistent with the observation that PCs are a form of ER-positive breast cancer with an excellent outcome (Rakha et al., 2011), given that the expression levels of proliferation-related genes have been shown to constitute one of the strongest predictors of outcome of ER-positive breast cancers (Reis-Filho and Pusztai, 2011). Other genes expressed at significantly lower levels in PCs than in grade- and ER-matched IDC-NSTs included those involved in cell assembly and organization (e.g. LAMB1, ACTN1 and collagen genes such as COL1A2, COL6A1, COL8A1, COL12A1, right-tailed Fisher exact test p-value<0.0001, Figure 2B) and cellular movement and migration (e.g. MMP3, MMP7 and THBS4, right-tailed Fisher exact test p-value<0.0001, Figure 2C). Consistent with these observations, DAVID KEGG pathway analysis revealed that the “cell adhesion molecules” (CAMs) pathway was the most significantly enriched for genes expressed at lower levels in PCs than in IDC-NSTs (data not shown). By contrast, 15 genes involved in cellular homeostasis (e.g. QSOX1) and angiogenesis (e.g. VEGFA, ESM1, SLC4A11 and VCAM1) were expressed at significantly higher levels in PCs than in grade- and ER-matched IDC-NSTs (Supplementary Table S5).

View Article: PubMed Central - PubMed

ABSTRACT

Papillary carcinoma (PC) is a rare type of breast cancer, which comprises three histologic subtypes: encapsulated PC (EPC), solid PC (SPC) and invasive PC (IPC). Microarray-based gene expression and Affymetrix SNP 6.0 gene copy number profiling, and RNA-sequencing revealed that PCs are luminal breast cancers that display transcriptomic profiles distinct from those of grade- and estrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs), and that the papillary histologic pattern is unlikely to be underpinned by a highly recurrent expressed fusion gene or a highly recurrent expressed mutation. Despite displaying similar patterns of gene copy number alterations, significant differences in the transcriptomic profiles of EPCs, SPCs and IPCs were found, and may account for their different histologic features.

No MeSH data available.


Related in: MedlinePlus