17p12 deletion in breast cancer predicts resistance to neoadjuvant chemotherapy

Wonshik Han, Jung Hoon Woo, Yoon Kyung Jeon, Song Ju Yang, Jihyoung Cho, Eunyoung Ko, Tae you Kim, Seock Ah Im, Do Youn Oh, In Ae Park, Ki Tae Hwang, Hyeong Gon Moon, Kap Seok Yang, Dong Young Noh

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Numerous studies have attempted to identify gene expression profiles which can be utilized to predict responses to neoadjuvant chemotherapy (NAC), but their findings are not clinically applicable at present. In the present study, we sought to determine DNA copy number alterations (CNAs) in breast cancer tissues which are associated with the response to NAC. Frozen tumor tissues from 63 breast cancer patients were obtained using core needle biopsy prior to NAC (3 cycles of docetaxel plus adriamycin) and were microdissected. Array comparative genomic hybridization (array CGH) with 4,045 bacterial artificial chromosome (BAC) probes was performed to identify the CNAs. Changes in tumor size in response to NAC were measured via magnetic resonance imaging. Fluorescence in situ hybridization (FISH) was conducted to verify array CGH results and for independent validation studies. CNAs at eight chromosomal loci encompassing 24 clones were correlated with changes in tumor size after NAC (p<0.05; t-test). Two CNAs were selected, 17p12 deletion and 17q21.32-33 gain, which were significantly associated with a smaller reduction in tumor size following NAC, via prioritization of the regions containing the candidate genes. In an independent validation set of samples from 39 patients, FISH assay further showed that the 17p12 deletion was markedly associated with smaller changes in tumor size (p=0.006), while the 17q21.32-33 gain was not significant (p=0.309). In conclusion, we successfully identified a 17p12 deletion in breast cancer tissue which can be applied in predicting tumor resistance to NAC.

Original languageEnglish
Pages (from-to)799-804
Number of pages6
JournalExperimental and Therapeutic Medicine
Volume2
Issue number5
DOIs
StatePublished - 1 Sep 2011

Fingerprint

Breast Neoplasms
Drug Therapy
Neoplasms
Comparative Genomic Hybridization
docetaxel
Fluorescence In Situ Hybridization
Large-Core Needle Biopsy
Bacterial Artificial Chromosomes
Validation Studies
Transcriptome
Doxorubicin
Clone Cells
Magnetic Resonance Imaging
DNA
Genes

Keywords

  • Breast neoplasms
  • Comparative genomic hybridization
  • Copy number
  • Microarray
  • Neoadjuvant chemotherapy
  • Predictive marker

Cite this

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title = "17p12 deletion in breast cancer predicts resistance to neoadjuvant chemotherapy",
abstract = "Numerous studies have attempted to identify gene expression profiles which can be utilized to predict responses to neoadjuvant chemotherapy (NAC), but their findings are not clinically applicable at present. In the present study, we sought to determine DNA copy number alterations (CNAs) in breast cancer tissues which are associated with the response to NAC. Frozen tumor tissues from 63 breast cancer patients were obtained using core needle biopsy prior to NAC (3 cycles of docetaxel plus adriamycin) and were microdissected. Array comparative genomic hybridization (array CGH) with 4,045 bacterial artificial chromosome (BAC) probes was performed to identify the CNAs. Changes in tumor size in response to NAC were measured via magnetic resonance imaging. Fluorescence in situ hybridization (FISH) was conducted to verify array CGH results and for independent validation studies. CNAs at eight chromosomal loci encompassing 24 clones were correlated with changes in tumor size after NAC (p<0.05; t-test). Two CNAs were selected, 17p12 deletion and 17q21.32-33 gain, which were significantly associated with a smaller reduction in tumor size following NAC, via prioritization of the regions containing the candidate genes. In an independent validation set of samples from 39 patients, FISH assay further showed that the 17p12 deletion was markedly associated with smaller changes in tumor size (p=0.006), while the 17q21.32-33 gain was not significant (p=0.309). In conclusion, we successfully identified a 17p12 deletion in breast cancer tissue which can be applied in predicting tumor resistance to NAC.",
keywords = "Breast neoplasms, Comparative genomic hybridization, Copy number, Microarray, Neoadjuvant chemotherapy, Predictive marker",
author = "Wonshik Han and Woo, {Jung Hoon} and Jeon, {Yoon Kyung} and Yang, {Song Ju} and Jihyoung Cho and Eunyoung Ko and Kim, {Tae you} and Im, {Seock Ah} and Oh, {Do Youn} and Park, {In Ae} and Hwang, {Ki Tae} and Moon, {Hyeong Gon} and Yang, {Kap Seok} and Noh, {Dong Young}",
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17p12 deletion in breast cancer predicts resistance to neoadjuvant chemotherapy. / Han, Wonshik; Woo, Jung Hoon; Jeon, Yoon Kyung; Yang, Song Ju; Cho, Jihyoung; Ko, Eunyoung; Kim, Tae you; Im, Seock Ah; Oh, Do Youn; Park, In Ae; Hwang, Ki Tae; Moon, Hyeong Gon; Yang, Kap Seok; Noh, Dong Young.

In: Experimental and Therapeutic Medicine, Vol. 2, No. 5, 01.09.2011, p. 799-804.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 17p12 deletion in breast cancer predicts resistance to neoadjuvant chemotherapy

AU - Han, Wonshik

AU - Woo, Jung Hoon

AU - Jeon, Yoon Kyung

AU - Yang, Song Ju

AU - Cho, Jihyoung

AU - Ko, Eunyoung

AU - Kim, Tae you

AU - Im, Seock Ah

AU - Oh, Do Youn

AU - Park, In Ae

AU - Hwang, Ki Tae

AU - Moon, Hyeong Gon

AU - Yang, Kap Seok

AU - Noh, Dong Young

PY - 2011/9/1

Y1 - 2011/9/1

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AB - Numerous studies have attempted to identify gene expression profiles which can be utilized to predict responses to neoadjuvant chemotherapy (NAC), but their findings are not clinically applicable at present. In the present study, we sought to determine DNA copy number alterations (CNAs) in breast cancer tissues which are associated with the response to NAC. Frozen tumor tissues from 63 breast cancer patients were obtained using core needle biopsy prior to NAC (3 cycles of docetaxel plus adriamycin) and were microdissected. Array comparative genomic hybridization (array CGH) with 4,045 bacterial artificial chromosome (BAC) probes was performed to identify the CNAs. Changes in tumor size in response to NAC were measured via magnetic resonance imaging. Fluorescence in situ hybridization (FISH) was conducted to verify array CGH results and for independent validation studies. CNAs at eight chromosomal loci encompassing 24 clones were correlated with changes in tumor size after NAC (p<0.05; t-test). Two CNAs were selected, 17p12 deletion and 17q21.32-33 gain, which were significantly associated with a smaller reduction in tumor size following NAC, via prioritization of the regions containing the candidate genes. In an independent validation set of samples from 39 patients, FISH assay further showed that the 17p12 deletion was markedly associated with smaller changes in tumor size (p=0.006), while the 17q21.32-33 gain was not significant (p=0.309). In conclusion, we successfully identified a 17p12 deletion in breast cancer tissue which can be applied in predicting tumor resistance to NAC.

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KW - Neoadjuvant chemotherapy

KW - Predictive marker

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