Genomic alterations during the in situ to invasive ductal breast carcinoma transition shaped by the immune system
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE144020 | GEO | 2020/12/01
REPOSITORIES: GEO
Similar Datasets
Project description:Genomic alterations during the in situ to invasive ductal breast carcinoma transition shaped by the immune system
| PRJNA602512 | ENA
Project description:The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and recurrent IDC. We demonstrate through combined copy-number and mutational analysis that recurrent IDC can be genetically related to its pure DCIS despite long latency periods and therapeutic interventions. Immune "hot" and "cold" tumors can arise as early as DCIS and are subtype-specific. Topologic analysis showed a similar degree of pan-leukocyte-tumor mixing in both DCIS and IDC but differ when assessing specific immune subpopulations such as CD4 T cells and CD68 macrophages. Tumor-specific copy-number aberrations in MHC-I presentation machinery and losses in 3p, 4q, and 5p are associated with differences in immune signaling in estrogen receptor (ER)-negative IDC. Common oncogenic hotspot mutations in genes including TP53 and PIK3CA are predicted to be neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition, and are associated with differences in immune signaling. We highlight both tumor and immune-specific changes in the transition of pure DCIS to IDC, including genetic changes in tumor cells that may have a role in modulating immune function and assist in immune escape, driving the transition to IDC. IMPLICATIONS: We demonstrate that the in situ to IDC evolutionary bottleneck is shaped by both tumor and immune cells.
| S-EPMC8026652 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE41194: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 1) GSE41196: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 2) GSE41197: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 3) GSE41198: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 4 stroma) GSE41227: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 4 Epithelial) Refer to individual Series
2012-09-29 | E-GEOD-41228 | biostudies-arrayexpress
Project description:This is a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive component (IDC) of nine breast ductal carcinoma to identify novel molecular markers characterizing the transition from DCIS to IDC for a better understanding of its molecular biology. Keywords: Affymetrix-based Microarrays in Mamma carcinoma
2006-05-24 | GSE3893 | GEO
Project description:Ductal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue samples from epithelium and stroma in normal breast, pure DCIS, and pure IBC were employed to define key gene expression profiles associated with disease progression.
2012-04-01 | GSE33692 | GEO
Project description:This is a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive component (IDC) of nine breast ductal carcinoma to identify novel molecular markers characterizing the transition from DCIS to IDC for a better understanding of its molecular biology.
2007-10-02 | E-GEOD-3893 | biostudies-arrayexpress
Project description:Ductal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue samples from epithelium and stroma in normal breast, pure DCIS, and pure IBC were employed to define key gene expression profiles associated with disease progression. Tumor and matching stroma were profiled for 9 DCIS patients, 10 IBC patients, and 3 normal breast. Differential gene expression was evaluated for paired normal stroma versus normal epitelium samples, paired DCIS stroma versus DCIS epitelium samples, paired IBC stroma versus IBC epitelium, IBC stroma versus DCIS stroma, and IBC epithelium versus DCIS epithelium.
2012-03-31 | E-GEOD-33692 | biostudies-arrayexpress
Project description:Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT-PCR was used for validation. All DCIS and invasive samples could be classified into the intrinsic molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DCIS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER-status and HER2-status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT-PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re-organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman's risk of progression, and lead to improved management that would avoid the current over- and under-treatment of patients. Breast cancer samples, 31 pure DCIS patients, 36 IDC patients, 42 mixed and 6 normal.
2010-12-24 | E-GEOD-26304 | biostudies-arrayexpress
Project description:In the breast, the reduction of invasive ductal carcinoma (IDC) seems to be smaller than expected from an increasing number of ductal carcinoma in situ (DCIS) detection in screening programs, suggesting that some DCIS lesions remain dormant and take a very long time for progression to IDC. However, the progression risk of individual DCIS and papilloma to IDC largely remain unassessable. To tackle this problem, we applied array-based comparative genomic hybridization to DCIS, IDC and papilloma lesions. We confirmed the presence of chromosomal copy-number alterations (CNAs) reported previously in breast cancers and the absence of chromosomal CNAs in the papillomas examined. These findings suggest that gene CNA profile is a good lineage marker for prediction of progression risk of individual tumors and that tumor progression within each lineage is driven by epigenetic rather than genetic alterations.
2016-09-16 | GSE86988 | GEO
Project description:To dissect mechanisms of immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinomas in situ (DCIS), and HER2+ and triple negative invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Analysis of gene expression profiles of T cells demonstrated enrichment for activated GZMB+MKI67+CD8+ effector T cell signatures in DCIS. TCR clonotypes also showed highest diversity in DCIS. Naïve T cell signatures predominated IDCs, especially triple negative subtypes. TIGIT and PDL1 immune checkpoint proteins showed differential expression between DCIS and IDCs with amplification of CD274 (encoding PDL1) only detected in triple negative IDCs. Our results imply that DCIS progression is limited by an anti-tumor immune response that becomes muted in invasive tumors due to selection for cancer cells and microenvironment that suppress activated T cells or no longer trigger their activation.
2017-06-28 | GSE87517 | GEO