PMID- 7473818
OWN - NLM
STAT- MEDLINE
DCOM- 19951130
LR  - 20190512
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 87
IP  - 22
DP  - 1995 Nov 15
TI  - Characterization of extensive genetic alterations in ductal carcinoma in situ by 
      fluorescence in situ hybridization and molecular analysis.
PG  - 1694-704
AB  - BACKGROUND: The molecular genetic analysis of invasive breast cancer has 
      identified breast cancer as a genetically complex disease. Ductal carcinoma in 
      situ (DCIS) is thought to represent a preinvasive step in breast cancer 
      progression, yet we know little about its biologic behavior or the genetic 
      alterations present. Because of the increasing diagnosis of DCIS by mammography 
      screening and the debate over how DCIS should be managed, there is a clear need 
      to define the molecular events underlying the development of DCIS. PURPOSE: Our 
      purpose was to identify patterns of genetic alterations in DCIS. METHODS: A group 
      of 30 formalin-fixed, paraffin-embedded blocks of tissue collected from 1987 
      through 1989 from 21 patients with DCIS was studied. Chromosomal imbalances were 
      determined by interphase cytogenetic analysis using the fluorescence in situ 
      hybridization (FISH) technique. DNA probes were used that recognize 
      chromosome-specific repetitive sequence loci at the centromeres of chromosomes 1, 
      3, 4, 6, 7, 8, 9, 10, 11, 16, 17, and 18. FISH was also used to detect ERBB2 gene 
      amplification in DCIS. To complement the FISH studies, microsatellite analysis of 
      markers near the BRCA1 region of chromosome 17 was done on tissue microdissected 
      from multiple areas of DCIS. Chromosomal imbalances were determined by 
      comparisons of chromosomal indices (total number of hybridization spots per total 
      number of nuclei counted) of normal and DCIS tissue, using the two-sided 
      Mann-Whitney test. RESULTS: Using FISH, we have identified patterns of DNA loss 
      and gain of certain chromosome-specific centromeric markers in DCIS. We observed 
      frequent gains of markers on chromosomes 3, 10, and 17 as well as loss of 
      chromosome 18-specific centromeric sequences. ERBB2 gene amplification was 
      detected in tumors from four of 15 patients studied and was clearly limited to 
      the tumor cells within the ducts. Because of the availability of topologically 
      distinct regions of tumors from individuals, we were able to show that paired 
      tumor specimens from individuals share genetic alterations and also have unique 
      ones, suggesting clonal diversity within tumors. The combination of FISH and 
      microsatellite analyses suggested that alterations in chromosome 17 may be quite 
      complex; three of five patients whose samples were analyzed had allelic imbalance 
      at markers on the long arm of chromosome 17. CONCLUSIONS: FISH and microsatellite 
      analyses are useful in detecting extensive genetic alterations in DCIS. 
      Examinations of DCIS tissue using these techniques have identified chromosomes 1, 
      3, 10, 16, 17, and 18 as candidate sites worthy of immediate study. IMPLICATIONS: 
      This approach may give direction to future research aimed at precisely mapping 
      loci altered in DCIS and help in understanding the biologic events associated 
      with tumor progression or recurrence.
FAU - Murphy, D S
AU  - Murphy DS
AD  - CRC Department of Medical Oncology, University of Glasgow, Cancer Research 
      Campaign Beatson Laboratories, Bearsden, Scotland.
FAU - Hoare, S F
AU  - Hoare SF
FAU - Going, J J
AU  - Going JJ
FAU - Mallon, E E
AU  - Mallon EE
FAU - George, W D
AU  - George WD
FAU - Kaye, S B
AU  - Kaye SB
FAU - Brown, R
AU  - Brown R
FAU - Black, D M
AU  - Black DM
FAU - Keith, W N
AU  - Keith WN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (DNA Probes)
RN  - 0 (DNA, Neoplasm)
SB  - IM
MH  - Breast Neoplasms/*genetics/pathology
MH  - Carcinoma in Situ/*genetics/pathology
MH  - Carcinoma, Ductal, Breast/*genetics/pathology
MH  - DNA Probes
MH  - DNA, Neoplasm/*genetics
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interphase/*genetics
MH  - Repetitive Sequences, Nucleic Acid/genetics
EDAT- 1995/11/15 00:00
MHDA- 1995/11/15 00:01
CRDT- 1995/11/15 00:00
PHST- 1995/11/15 00:00 [pubmed]
PHST- 1995/11/15 00:01 [medline]
PHST- 1995/11/15 00:00 [entrez]
AID - 10.1093/jnci/87.22.1694 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 1995 Nov 15;87(22):1694-704. doi: 10.1093/jnci/87.22.1694.