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Tiling array-CGH for the assessment of genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs.

Brommesson, Sara LU ; Jönsson, Göran B LU ; Forsare, Carina LU ; Grabau, Dorthe LU ; Malmström, Per LU ; Ringnér, Markus LU ; Fernö, Mårten LU and Hedenfalk, Ingrid LU (2008) In BMC Clinical Pathology 8(July 10).
Abstract
ABSTRACT: BACKGROUND: Today, no objective criteria exist to differentiate between individual primary tumors and intra- or intermammary dissemination respectively, in patients diagnosed with two or more synchronous breast cancers. To elucidate whether these tumors most likely arise through clonal expansion, or whether they represent individual primary tumors is of tumor biological interest and may have clinical implications. In this respect, high resolution genomic profiling may provide a more reliable approach than conventional histopathological and tumor biological factors. METHODS: 32 K tiling microarray-based comparative genomic hybridization (aCGH) was used to explore the genomic similarities among synchronous unilateral and bilateral... (More)
ABSTRACT: BACKGROUND: Today, no objective criteria exist to differentiate between individual primary tumors and intra- or intermammary dissemination respectively, in patients diagnosed with two or more synchronous breast cancers. To elucidate whether these tumors most likely arise through clonal expansion, or whether they represent individual primary tumors is of tumor biological interest and may have clinical implications. In this respect, high resolution genomic profiling may provide a more reliable approach than conventional histopathological and tumor biological factors. METHODS: 32 K tiling microarray-based comparative genomic hybridization (aCGH) was used to explore the genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was compared with histopathological and tumor biological parameters. RESULTS: Based on global copy number profiles and unsupervised hierarchical clustering, five of ten (p = 1.9 x 10-5) unilateral tumor pairs displayed similar genomic profiles within the pair, while only one of eight bilateral tumor pairs (p = 0.29) displayed pair-wise genomic similarities. DNA index, histological type and presence of vessel invasion correlated with the genomic analyses. CONCLUSION: Synchronous unilateral tumor pairs are often genomically similar, while synchronous bilateral tumors most often represent individual primary tumors. However, two independent unilateral primary tumors can develop synchronously and contralateral tumor spread can occur. The presence of an intraductal component is not informative when establishing the independence of two tumors, while vessel invasion, the presence of which was found in clustering tumor pairs but not in tumor pairs that did not cluster together, supports the clustering outcome. Our data suggest that genomically similar unilateral tumor pairs may represent a more aggressive disease that requires the addition of more severe treatment modalities, and underscores the importance of evaluating the clonality of multiple tumors for optimal patient management. In summary, our findings demonstrate the importance of evaluating the properties of both tumors in order to determine the most optimal patient management. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Clinical Pathology
volume
8
issue
July 10
publisher
BioMed Central
external identifiers
  • PMID:18616792
  • Scopus:47649128110
ISSN
1472-6890
DOI
10.1186/1472-6890-8-6
project
CREATE Health
language
English
LU publication?
yes
id
44ae1301-3851-44b6-91b2-5ddf9d752391 (old id 1181286)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18616792?dopt=Abstract
date added to LUP
2008-08-07 13:38:49
date last changed
2017-01-15 04:28:53
@article{44ae1301-3851-44b6-91b2-5ddf9d752391,
  abstract     = {ABSTRACT: BACKGROUND: Today, no objective criteria exist to differentiate between individual primary tumors and intra- or intermammary dissemination respectively, in patients diagnosed with two or more synchronous breast cancers. To elucidate whether these tumors most likely arise through clonal expansion, or whether they represent individual primary tumors is of tumor biological interest and may have clinical implications. In this respect, high resolution genomic profiling may provide a more reliable approach than conventional histopathological and tumor biological factors. METHODS: 32 K tiling microarray-based comparative genomic hybridization (aCGH) was used to explore the genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was compared with histopathological and tumor biological parameters. RESULTS: Based on global copy number profiles and unsupervised hierarchical clustering, five of ten (p = 1.9 x 10-5) unilateral tumor pairs displayed similar genomic profiles within the pair, while only one of eight bilateral tumor pairs (p = 0.29) displayed pair-wise genomic similarities. DNA index, histological type and presence of vessel invasion correlated with the genomic analyses. CONCLUSION: Synchronous unilateral tumor pairs are often genomically similar, while synchronous bilateral tumors most often represent individual primary tumors. However, two independent unilateral primary tumors can develop synchronously and contralateral tumor spread can occur. The presence of an intraductal component is not informative when establishing the independence of two tumors, while vessel invasion, the presence of which was found in clustering tumor pairs but not in tumor pairs that did not cluster together, supports the clustering outcome. Our data suggest that genomically similar unilateral tumor pairs may represent a more aggressive disease that requires the addition of more severe treatment modalities, and underscores the importance of evaluating the clonality of multiple tumors for optimal patient management. In summary, our findings demonstrate the importance of evaluating the properties of both tumors in order to determine the most optimal patient management.},
  articleno    = {6},
  author       = {Brommesson, Sara and Jönsson, Göran B and Forsare, Carina and Grabau, Dorthe and Malmström, Per and Ringnér, Markus and Fernö, Mårten and Hedenfalk, Ingrid},
  issn         = {1472-6890},
  language     = {eng},
  number       = {July 10},
  publisher    = {BioMed Central},
  series       = {BMC Clinical Pathology},
  title        = {Tiling array-CGH for the assessment of genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs.},
  url          = {http://dx.doi.org/10.1186/1472-6890-8-6},
  volume       = {8},
  year         = {2008},
}