Breast cancer metastases are molecularly distinct from their primary tumors

Vecchi, Manuela; Confalonieri, Stefano; Nuciforo, Paolo; Viganò, Mauro; Capra, Maria; Bianchi, M.; Nicosia, Daniela; Bianchi, Fabrizio; Galimberti, Viviana; Viale, Giuseppe; Palermo, Giuseppe; Riccardi, Alessandro; Campanini, R.; Daidone, Maria Grazia; Pierotti, Marco A.; Pece, Salvatore; Fiore, Pier Paolo Di

doi:10.1038/sj.onc.1210858

Cited by 115 publications

(100 citation statements)

References 40 publications

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“…Third, ISH/TMA can be carried out on archival paraffin-embedded samples, which is extremely advantageous for validation studies on large case collections for which patient follow-up is available. Fourth, we have already used ISH/TMA for large screening projects and showed that its results correlate well with those obtainable with more quantitative methods, such as quantitative PCR (Nicassio et al, 2005;Capra et al, 2006;Vecchi et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor

et al. 2009

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Protein ubiquitination is critical for many cellular processes, through its ability to regulate protein degradation and various signaling mechanisms. In the ubiquitin (Ub) system, substrate specificity is achieved through the E3 family of Ub ligases. Because alterations of the ubiquitination machinery have been reported in human cancers, the selective interference with Ub ligases might represent a powerful therapeutic tool. Here, we report the first wide survey of misregulation of Ub ligases in cancer. We analysed 82 Ub ligases in nine types of cancer by in situ hybridization on tissue microarrays. We found 27 instances in which an Ub ligase was altered in a given type of tumor, when compared with normal tissues: 21 cases of overexpression and 6 cases of underexpression. We further analysed selected Ub ligases in large cohorts of breast and non-small-cell lung carcinomas. In five, of six, of these extended analyses (HUWE1, CCNB1IP1, SIAH1 and SIAH2 in breast cancer and CCNB1IP1 in lung cancer), we found that the levels of Ub ligases correlated significantly with relevant prognostic factors, and with clinical outcome. Our findings show that the alteration of Ub ligases is a frequent event in cancer and identify candidate targets for molecular therapies.

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Section: Methodsmentioning

confidence: 99%

Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor

et al. 2009

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“…[23][24][25][26]33,34 Many factors can be responsible for this incongruence: both related to the still poorly understood biology and a well-recognized heterogeneity of the disease, low numbers of studied patients as well as factors related to the differences in the methodology. Our results from the analysis of DNA copy number actually support both conclusions.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, a few of these located at chromosomes 1, 4, 8 and 11 and represented as gains or amplifications were shared by up to four patients, and were characterized by a high level of difference between metastasis and primary tumor. The majority of these regions encompassed genes for which DNA amplification is strongly correlated with overexpression, and genes that have been previously shown as differentially expressed in metastasis relative to primary tumor [20][21][22][23][24][25][26] (Table 3; Supplementary Table 2). For example, an aberrant region unique to class II at 6q15-6q16 (87.55-97.56 Mb) and exclusively deleted in metastasis of breast cancer contains candidate tumor suppressor genes described earlier for prostate cancer: PNRC1 and CASP8AP2.…”

Section: Comparisons Of Genomic Profiles For Matched Primary Tumors Amentioning

confidence: 99%

Frequent genetic differences between matched primary and metastatic breast cancer provide an approach to identification of biomarkers for disease progression

et al. 2010

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Breast cancer is a major cause of morbidity and mortality in women and its metastatic spread is the principal reason behind the fatal outcome. Metastasis-related research of breast cancer is however underdeveloped when compared with the abundant literature on primary tumors. We applied an unexplored approach comparing at high resolution the genomic profiles of primary tumors and synchronous axillary lymph node metastases from 13 patients with breast cancer. Overall, primary tumors displayed 20% higher number of aberrations than metastases. In all but two patients, we detected in total 157 statistically significant differences between primary lesions and matched metastases. We further observed differences that can be linked to metastatic disease and there was also an overlapping pattern of changes between different patients. Many of the differences described here have been previously linked to poor patient survival, suggesting that this is a viable approach toward finding biomarkers for disease progression and definition of new targets useful for development of anticancer drugs. Frequent genetic differences between primary tumors and metastases in breast cancer also question, at least to some extent, the role of primary tumors as a surrogate subject of study for the systemic disease.

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“…In a study using microarray technology, researchers demonstrated that gene expression profiles of cells from primary cancer tissues and ALNs share high similarities (13). However, other studies demonstrated otherwise claiming that metastasized cells in the ALNs display major differences than their primary look-alikes at the molecular level (15)(16)(17)(18). There are studies investigated breast tumor tissues and their ALNs to which tumor was metastasized.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of a Conserved Proteomic Pattern of Breast Cancer Tissue and Metastatic Axillary Lymph Node

Akpınar¹,

Şimşek²,

Guler³

et al. 2017

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RezumatObiectiv: Cancerul de sân este unul dintre cele mai devastatoare tipuri de cancer care afectează femeile. Pentru luarea deciziilor critice cu privire la soarta ţesutului mamar canceros, este necesară evaluarea implicării ganglionilor limfatici axilari (ALN). Cu toate acestea, o astfel de implicare ALN este dificil de prezis fără intervenţia chirurgicală. Prin urmare, un test uşor de predicţie care utilizează markeri de proteine poate fi o abordare dorită. În acest studiu, am efectuat o analiză completă a proteinomei pentru a descoperi modelul de exprimare a proteinelor legate de tumori în cancerul de sân primar. Metode şi Materiale: Proteinele au fost extrase din ţesuturile tumorale şi au fost supuse unei electroforeze în gel de poliacrilamidă în două dimensiuni (2D). Imaginile de gel rezultate au fost utilizate pentru compararea spoturilor inter-gel utilizând software-ul PDQuest Advance. Modelele obţinute au fost utilizate pentru diferenţierea tipurilor tumorale invazive de la cele neinvazive. Rezultate: 24 de pete de proteine conservate ale căror intensităţi au fost moderat reglementate înalt pe geluri. Aceste pete de proteine au fost folosite pentru a crea un model conservat 2D care acoperă un interval de pH de la 4 la 8. Concluzie: Punctele proteice care generează un model conservat între cancerul de sân primar şi ganglionul limfatic axilar au indicat că o abordare proteomică robustă şi foarte fiabilă, de exemplu 2DE, poate fi utilizată pentru a diferenţia forme metastatice de cancer de sân de la cele nemetastatice. Elucidation of a Conserved Proteomic Pattern of Breast Original ArticleCuvinte cheie: cancer de sân, axilar, ganglion limfatic, 2D, proteomică AbstractObjective: Breast cancer is one of the most devastating cancer types affecting women. For critical decision making regarding the fate of cancerous breast tissue, the assessment of axillary lymph node (ALN) involvement is required. However, such ALN involvement is difficult to predict without surgical intervention. Therefore, an easy predictive test using protein markers may be a desirable approach. In this study, we performed a whole proteome analysis to reveal the presence of a putative biomarker panel using primary breast tumor tissue. Materials and Methods: Proteins were extracted from tumor tissues and were subjected to two dimensional (2D) gel electrophoresis. The resulting gel images were used for inter-gel spot comparisons using PDQuest Advance software. The paterns thus obtained were used for differentiating invasive tumor types from non-invasive ones.Results: The analysis of 2D gel images revealed the presence of 24 conserved protein spots whose intensities were moderately regulated high on the gels. Those protein spots were used to create a conserved 2D pattern spanning a pH range of 4 to 8. Conclusion: Protein spots generating a preserved model among pattern between primary breast cancer and its axillary lymph node indicated that a robust and highly reliable proteomic approach, e.g., 2DE may be used to differentiate metastatic fo...

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Breast cancer metastases are molecularly distinct from their primary tumors

Cited by 115 publications

References 40 publications

Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor

Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor

Frequent genetic differences between matched primary and metastatic breast cancer provide an approach to identification of biomarkers for disease progression

Elucidation of a Conserved Proteomic Pattern of Breast Cancer Tissue and Metastatic Axillary Lymph Node

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