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| Status |
Public on Aug 01, 2006 |
| Title |
High resolution analysis of early lobular neoplastic breast lesions (ALH and LCIS) by whole genome tiling path array CGH |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
The identification of genomic alterations occurring in neoplastic lesions provides insight into both lesion occurrence and disease progression. In this study we used microarray comparative genomic hybridization (CGH) to investigate genetic changes in atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), as the presence of these lobular neoplastic lesions is an indicator of risk in the development of invasive breast cancer. DNA was extracted from microdissected archival breast tissue containing ALH or LCIS, lacking adjacent invasive carcinoma, and subjected to whole-genome tiling path microarray-CGH using the submegabase resolution tiling set (SMRTr)-array platform. Twelve ALH and 13 LCIS lesions were examined. Copy number alterations were identified using statistical criteria and validated with Real-Time PCR and fluorescence in situ hybridization. From statistical analysis, a greater number of alterations were observed in ALH compared to LCIS. Alterations common to ALH include gain at 2p11.2 and loss at 7p11.2-p11.1 and 22q11.1. Alterations common to LCIS include gain at 20q13.13 and loss at 19q13.2-q13.31. In both ALH and LCIS, we observed loss of 16q21-q23.1, an altered region previously identified in lobular neoplasia and invasive carcinoma. The validation of select alterations reinforces the genomic signature. This study represents the first whole-genome investigation of lobular neoplastic breast lesions using clinical archival specimens. The identified genomic signature includes copy number alterations not previously identified for lobular neoplasia. This genomic signature, common to ALH and LCIS, suggests a role for the acquisition of novel genomic alterations in the aberrant cellular proliferation that defines lobular neoplasia.
Keywords: comparative genomic hybridization, high resolution analysis of atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) human archival breast lesions by whole genome tiling path array CGH
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| Overall design |
25 early lobular neoplastic breast lesions (atypical lobular hyperplasia, ALH; lobular carcinoma in situ, LCIS) were differentially labeled and each competitively hybridized against female genomic DNA using the (27K) SMRTr tiling array
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| Contributor(s) |
Mastracci TL, Shadeo A, Colby SM, Tuck AB, O'Malley FP, Bull SB, Lam WL, Andrulis IL |
| Citation missing |
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| |
| Submission date |
Mar 31, 2006 |
| Last update date |
Mar 16, 2012 |
| Contact name |
Teresa L Mastracci |
| E-mail(s) |
teresa.mastracci@gmail.com
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| Phone |
416-586-4800
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| Organization name |
Samuel Lunenfeld Research Institute
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| Department |
Mount Sinai Hospital
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| Lab |
Andrulis Lab
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| Street address |
600 University Ave., room 984
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| City |
Toronto |
| State/province |
ON |
| ZIP/Postal code |
M5G1X5 |
| Country |
Canada |
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| Platforms (1) |
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| Samples (25)
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| Relations |
| BioProject |
PRJNA94445 |
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