Intratumor genetic heterogeneity of breast carcinomas as determined by fine needle aspiration and TaqMan low density array

Maria B. Lyng, Anne-Vibeke Laenkholm, Niels Pallisgaard, Werner Vach, Ann Knoop, Martin Bak, Henrik Ditzel

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

 
Udgivelsesdato: 2007-null
OriginalsprogEngelsk
TidsskriftAnalytical Cellular Pathology
Vol/bind29
Udgave nummer5
Sider (fra-til)361-372
Antal sider12
ISSN2210-7177
StatusUdgivet - 1. jan. 2007

Fingeraftryk

Genetic Heterogeneity
Neoplasms
Transcriptome
Cluster Analysis
Neoadjuvant Therapy
Gene Expression Profiling
RNA
Polymerase Chain Reaction

Citer dette

Lyng, Maria B. ; Laenkholm, Anne-Vibeke ; Pallisgaard, Niels ; Vach, Werner ; Knoop, Ann ; Bak, Martin ; Ditzel, Henrik. / Intratumor genetic heterogeneity of breast carcinomas as determined by fine needle aspiration and TaqMan low density array. I: Analytical Cellular Pathology. 2007 ; Bind 29, Nr. 5. s. 361-372.
@article{6e994b70cb2911dc8674000ea68e967b,
title = "Intratumor genetic heterogeneity of breast carcinomas as determined by fine needle aspiration and TaqMan low density array",
abstract = "BACKGROUND: Gene expression profiling is thought to be an important tool in determining treatment strategies for breast cancer patients. Tissues for such analysis may at a preoperative stage be obtained, by fine needle aspiration (FNA) allowing initiation of neoadjuvant treatment. To evaluate the extent of the genetic heterogeneity within primary breast carcinomas, we examined whether a gene expression profile obtained by FNA was representative of the tumor. METHODS: Tumors from 12 consecutive cases of early predominantly estrogen receptor positive (ER+) breast cancer patients undergoing primary surgery were split in halves and FNAs were obtained from each half. A tissue biopsy of the tumors was also snap-frozen for comparison. Non-amplified RNA was investigated by the novel qRT-PCR-based technique, Low Density Array (LDA) using 4 reference genes and 44 target genes. RESULTS: Comparison of gene expression at the single gene level in the two FNA samples from each tumor demonstrated various degrees of heterogeneity. However, compared as gene expression profiles, intratumor correlations for 9/12 patients were high and these pairs could in a theoretical blinding of all the FNAs be correctly matched by statistical analysis. High correlations between the gene profiles of tumor FNAs and tissue biopsies from the same patient were observed for all patients. A cluster analysis identified clustering of both the two FNAs and the tissue biopsy of the same 9 patients. CONCLUSION: The overall genetic heterogeneity of breast carcinomas, as sampled by FNA, does not prohibit generation of useful gene profiles for treatment decision making. However, sampling and analysis strategies should take heterogeneity within a tumor, and varying heterogeneity amongst the single genes, into account",
author = "Lyng, {Maria B.} and Anne-Vibeke Laenkholm and Niels Pallisgaard and Werner Vach and Ann Knoop and Martin Bak and Henrik Ditzel",
year = "2007",
month = "1",
day = "1",
language = "English",
volume = "29",
pages = "361--372",
journal = "Analytical Cellular Pathology",
issn = "2210-7177",
publisher = "Hindawi Publishing Corporation",
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Intratumor genetic heterogeneity of breast carcinomas as determined by fine needle aspiration and TaqMan low density array. / Lyng, Maria B.; Laenkholm, Anne-Vibeke; Pallisgaard, Niels; Vach, Werner; Knoop, Ann; Bak, Martin; Ditzel, Henrik.

I: Analytical Cellular Pathology, Bind 29, Nr. 5, 01.01.2007, s. 361-372.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Intratumor genetic heterogeneity of breast carcinomas as determined by fine needle aspiration and TaqMan low density array

AU - Lyng, Maria B.

AU - Laenkholm, Anne-Vibeke

AU - Pallisgaard, Niels

AU - Vach, Werner

AU - Knoop, Ann

AU - Bak, Martin

AU - Ditzel, Henrik

PY - 2007/1/1

Y1 - 2007/1/1

N2 - BACKGROUND: Gene expression profiling is thought to be an important tool in determining treatment strategies for breast cancer patients. Tissues for such analysis may at a preoperative stage be obtained, by fine needle aspiration (FNA) allowing initiation of neoadjuvant treatment. To evaluate the extent of the genetic heterogeneity within primary breast carcinomas, we examined whether a gene expression profile obtained by FNA was representative of the tumor. METHODS: Tumors from 12 consecutive cases of early predominantly estrogen receptor positive (ER+) breast cancer patients undergoing primary surgery were split in halves and FNAs were obtained from each half. A tissue biopsy of the tumors was also snap-frozen for comparison. Non-amplified RNA was investigated by the novel qRT-PCR-based technique, Low Density Array (LDA) using 4 reference genes and 44 target genes. RESULTS: Comparison of gene expression at the single gene level in the two FNA samples from each tumor demonstrated various degrees of heterogeneity. However, compared as gene expression profiles, intratumor correlations for 9/12 patients were high and these pairs could in a theoretical blinding of all the FNAs be correctly matched by statistical analysis. High correlations between the gene profiles of tumor FNAs and tissue biopsies from the same patient were observed for all patients. A cluster analysis identified clustering of both the two FNAs and the tissue biopsy of the same 9 patients. CONCLUSION: The overall genetic heterogeneity of breast carcinomas, as sampled by FNA, does not prohibit generation of useful gene profiles for treatment decision making. However, sampling and analysis strategies should take heterogeneity within a tumor, and varying heterogeneity amongst the single genes, into account

AB - BACKGROUND: Gene expression profiling is thought to be an important tool in determining treatment strategies for breast cancer patients. Tissues for such analysis may at a preoperative stage be obtained, by fine needle aspiration (FNA) allowing initiation of neoadjuvant treatment. To evaluate the extent of the genetic heterogeneity within primary breast carcinomas, we examined whether a gene expression profile obtained by FNA was representative of the tumor. METHODS: Tumors from 12 consecutive cases of early predominantly estrogen receptor positive (ER+) breast cancer patients undergoing primary surgery were split in halves and FNAs were obtained from each half. A tissue biopsy of the tumors was also snap-frozen for comparison. Non-amplified RNA was investigated by the novel qRT-PCR-based technique, Low Density Array (LDA) using 4 reference genes and 44 target genes. RESULTS: Comparison of gene expression at the single gene level in the two FNA samples from each tumor demonstrated various degrees of heterogeneity. However, compared as gene expression profiles, intratumor correlations for 9/12 patients were high and these pairs could in a theoretical blinding of all the FNAs be correctly matched by statistical analysis. High correlations between the gene profiles of tumor FNAs and tissue biopsies from the same patient were observed for all patients. A cluster analysis identified clustering of both the two FNAs and the tissue biopsy of the same 9 patients. CONCLUSION: The overall genetic heterogeneity of breast carcinomas, as sampled by FNA, does not prohibit generation of useful gene profiles for treatment decision making. However, sampling and analysis strategies should take heterogeneity within a tumor, and varying heterogeneity amongst the single genes, into account

M3 - Journal article

VL - 29

SP - 361

EP - 372

JO - Analytical Cellular Pathology

JF - Analytical Cellular Pathology

SN - 2210-7177

IS - 5

ER -