PMID- 10214356
OWN - NLM
STAT- MEDLINE
DCOM- 19990507
LR  - 20190816
IS  - 0165-4608 (Print)
IS  - 0165-4608 (Linking)
VI  - 110
IP  - 2
DP  - 1999 Apr 15
TI  - Intratumoral heterogeneity in breast carcinoma revealed by laser-microdissection 
      and comparative genomic hybridization.
PG  - 94-102
AB  - To evaluate the potential cytogenetic heterogeneity in breast carcinoma, several 
      small cell groups (each consisting of 20 to 50 cells) were investigated within 
      paraffin sections. By laser-microdissection, three to seven cell groups were 
      taken per case. The DNA was amplified by degenerate oligonucleotide primed PCR 
      (DOP-PCR), and the samples were analyzed by CGH for chromosomal gains and losses. 
      Two ductal invasive breast carcinomas, one of them with two lymphnode metastases, 
      were investigated. To compare the results from the small samples, CGH was also 
      performed on DNA isolated from the tumorous regions of three to five serial 
      sections (10(7) to 10(6) cells). The aberrations observed in the microdissected 
      tumor samples were multiple and involved up to 14 different chromosomal or 
      subchromosomal regions. The most frequent changes were gains on chromosomes 12q 
      (14/20) and 20q (16/20), and loss on 13q (12/20). Some aberrations have rarely 
      been detected (e.g., loss on 2p, gain on 8q). Comparing chromosomal imbalances in 
      primary tumors and lymph node metastases, more consistent changes were found 
      between the primary tumor and its corresponding metastases than between both 
      primary tumors. The laser-microdissected samples in general showed more 
      chromosomal aberrations than DNA isolated from several tumor sections. Our CGH 
      results were confirmed by fluorescence in situ hybridization (FISH) for the 
      chromosomal regions of centromere 1 and 20, and 20q13. In addition, 
      microsatellite analyses on 31 samples confirmed our CGH findings for selected 
      chromosome regions 2p and 11q. It can be concluded that there is a distinct 
      intratumoral heterogeneity in primary breast tumors as well as in the 
      corresponding lymph node metastases. The combination of microdissection and CGH 
      enabled us to detect cytogenetic aberrations from important clones which are 
      missed when analyzing DNA extracted from large cell numbers.
FAU - Aubele, M
AU  - Aubele M
AD  - Institute of Pathology, GSF-National Research Center for Environment and Health, 
      Neuherberg, Germany.
FAU - Mattis, A
AU  - Mattis A
FAU - Zitzelsberger, H
AU  - Zitzelsberger H
FAU - Walch, A
AU  - Walch A
FAU - Kremer, M
AU  - Kremer M
FAU - Hutzler, P
AU  - Hutzler P
FAU - Hofler, H
AU  - Hofler H
FAU - Werner, M
AU  - Werner M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Neoplasm)
SB  - IM
MH  - Breast Neoplasms/*genetics
MH  - Carcinoma, Ductal, Breast/*genetics/secondary
MH  - Chromosome Aberrations
MH  - Chromosome Mapping/methods
MH  - DNA Primers/genetics
MH  - DNA, Neoplasm/genetics/isolation & purification
MH  - Dissection/methods
MH  - Female
MH  - Genetic Heterogeneity
MH  - *Histocytological Preparation Techniques
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - In Situ Hybridization/*methods
MH  - In Situ Hybridization, Fluorescence
MH  - Lasers
MH  - Loss of Heterozygosity
MH  - Lymphatic Metastasis
MH  - Microsatellite Repeats/genetics
MH  - Polymerase Chain Reaction/methods
EDAT- 1999/04/24 00:00
MHDA- 1999/04/24 00:01
CRDT- 1999/04/24 00:00
PHST- 1999/04/24 00:00 [pubmed]
PHST- 1999/04/24 00:01 [medline]
PHST- 1999/04/24 00:00 [entrez]
AID - S0165460898002052 [pii]
AID - 10.1016/s0165-4608(98)00205-2 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 1999 Apr 15;110(2):94-102. doi: 
      10.1016/s0165-4608(98)00205-2.