Array comparative genomic hybridization analysis discloses chromosome copy number alterations as indicators of patient outcome in lymph node-negative breast cancer

Ryoko Kikuchi-Koike, Kazunori Nagasaka, Hitoshi Tsuda, Yasuyuki Ishii, Masaru Sakamoto, Yoshihiro Kikuchi, Shiho Fukui, Yuko Miyagawa, Haruko Hiraike, Takayuki Kobayashi, Takayuki Kinoshita, Yae Kanai, Tatsuhiro Shibata, Issei Imoto, Johji Inazawa, Osamu Matsubara, Takuya Ayabe

研究成果: Article

抄録

Background: Patients with lymph node metastasis-negative (pN0) invasive breast cancer have favorable outcomes following initial treatment. However, false negatives which occur during routine histologic examination of lymph nodes are reported to underestimate the clinical stage of disease. To identify a high-risk group in pN0 invasive breast cancer, we examined copy number alterations (CNAs) of 800 cancer-related genes. Methods: Using array-based comparative genomic hybridization (CGH) in 51 pN0 cases (19 relapsed and 32 non-relapsed cases), the positivities of specific gene CNAs in the relapsed and non-relapsed groups were compared. An unsupervised hierarchical cluster analysis was then performed to identify case groups that were correlated with patient outcomes. Results: The cluster analysis identified three distinct clusters of cases: groups 1, 2, and 3. The major component was triple-negative cases (69%, 9 of 13) in group 1, luminal B-like (57%, 13 of 23) and HER2-overexpressing (26%, 6 of 23) subtypes in group 2, and luminal A-like subtype (60%, 9 of 15) in group 3. Among all 51 cases, those in group 1 showed significantly worse overall survival (OS) than group 2 (p = 0.014), and 5q15 loss was correlated with worse OS (p = 0.017). Among 19 relapsed cases, both OS and relapse-free survival (RFS) rates were significantly lower in group 1 than in group 2 (p = 0.0083 and 0.0018, respectively), and 5q15 loss, 12p13.31 gain, and absence of 16p13.3 gain were significantly correlated with worse OS and RFS (p = 0.019 and 0.0027, respectively). Conclusions: As the target genes in these loci, NR2F1 (5q15), TNFRSF1A (12p13.31), and ABCA3 (16p13.3) were examined. 5q15 loss, 12p13.31 gain, and absence of 16q13.3 gain were potential indicators of high-risk recurrence and aggressive clinical behavior of pN0 invasive breast cancers.

元の言語English
記事番号521
ジャーナルBMC Cancer
19
発行部数1
DOI
出版物ステータスPublished - 2019 5 30
外部発表Yes

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Comparative Genomic Hybridization
Chromosomes
Lymph Nodes
Breast Neoplasms
Survival
Recurrence
Cluster Analysis
Gene Dosage
Neoplasm Genes
Survival Rate
Neoplasm Metastasis
Genes

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

これを引用

Array comparative genomic hybridization analysis discloses chromosome copy number alterations as indicators of patient outcome in lymph node-negative breast cancer. / Kikuchi-Koike, Ryoko; Nagasaka, Kazunori; Tsuda, Hitoshi; Ishii, Yasuyuki; Sakamoto, Masaru; Kikuchi, Yoshihiro; Fukui, Shiho; Miyagawa, Yuko; Hiraike, Haruko; Kobayashi, Takayuki; Kinoshita, Takayuki; Kanai, Yae; Shibata, Tatsuhiro; Imoto, Issei; Inazawa, Johji; Matsubara, Osamu; Ayabe, Takuya.

:: BMC Cancer, 巻 19, 番号 1, 521, 30.05.2019.

研究成果: Article

Kikuchi-Koike, R, Nagasaka, K, Tsuda, H, Ishii, Y, Sakamoto, M, Kikuchi, Y, Fukui, S, Miyagawa, Y, Hiraike, H, Kobayashi, T, Kinoshita, T, Kanai, Y, Shibata, T, Imoto, I, Inazawa, J, Matsubara, O & Ayabe, T 2019, 'Array comparative genomic hybridization analysis discloses chromosome copy number alterations as indicators of patient outcome in lymph node-negative breast cancer', BMC Cancer, 巻. 19, 番号 1, 521. https://doi.org/10.1186/s12885-019-5737-7
Kikuchi-Koike, Ryoko ; Nagasaka, Kazunori ; Tsuda, Hitoshi ; Ishii, Yasuyuki ; Sakamoto, Masaru ; Kikuchi, Yoshihiro ; Fukui, Shiho ; Miyagawa, Yuko ; Hiraike, Haruko ; Kobayashi, Takayuki ; Kinoshita, Takayuki ; Kanai, Yae ; Shibata, Tatsuhiro ; Imoto, Issei ; Inazawa, Johji ; Matsubara, Osamu ; Ayabe, Takuya. / Array comparative genomic hybridization analysis discloses chromosome copy number alterations as indicators of patient outcome in lymph node-negative breast cancer. :: BMC Cancer. 2019 ; 巻 19, 番号 1.
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title = "Array comparative genomic hybridization analysis discloses chromosome copy number alterations as indicators of patient outcome in lymph node-negative breast cancer",
abstract = "Background: Patients with lymph node metastasis-negative (pN0) invasive breast cancer have favorable outcomes following initial treatment. However, false negatives which occur during routine histologic examination of lymph nodes are reported to underestimate the clinical stage of disease. To identify a high-risk group in pN0 invasive breast cancer, we examined copy number alterations (CNAs) of 800 cancer-related genes. Methods: Using array-based comparative genomic hybridization (CGH) in 51 pN0 cases (19 relapsed and 32 non-relapsed cases), the positivities of specific gene CNAs in the relapsed and non-relapsed groups were compared. An unsupervised hierarchical cluster analysis was then performed to identify case groups that were correlated with patient outcomes. Results: The cluster analysis identified three distinct clusters of cases: groups 1, 2, and 3. The major component was triple-negative cases (69{\%}, 9 of 13) in group 1, luminal B-like (57{\%}, 13 of 23) and HER2-overexpressing (26{\%}, 6 of 23) subtypes in group 2, and luminal A-like subtype (60{\%}, 9 of 15) in group 3. Among all 51 cases, those in group 1 showed significantly worse overall survival (OS) than group 2 (p = 0.014), and 5q15 loss was correlated with worse OS (p = 0.017). Among 19 relapsed cases, both OS and relapse-free survival (RFS) rates were significantly lower in group 1 than in group 2 (p = 0.0083 and 0.0018, respectively), and 5q15 loss, 12p13.31 gain, and absence of 16p13.3 gain were significantly correlated with worse OS and RFS (p = 0.019 and 0.0027, respectively). Conclusions: As the target genes in these loci, NR2F1 (5q15), TNFRSF1A (12p13.31), and ABCA3 (16p13.3) were examined. 5q15 loss, 12p13.31 gain, and absence of 16q13.3 gain were potential indicators of high-risk recurrence and aggressive clinical behavior of pN0 invasive breast cancers.",
keywords = "ABCA3, Array-CGH, NR2F1, pN0 invasive breast cancer, TNFRSF1A",
author = "Ryoko Kikuchi-Koike and Kazunori Nagasaka and Hitoshi Tsuda and Yasuyuki Ishii and Masaru Sakamoto and Yoshihiro Kikuchi and Shiho Fukui and Yuko Miyagawa and Haruko Hiraike and Takayuki Kobayashi and Takayuki Kinoshita and Yae Kanai and Tatsuhiro Shibata and Issei Imoto and Johji Inazawa and Osamu Matsubara and Takuya Ayabe",
year = "2019",
month = "5",
day = "30",
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language = "English",
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journal = "BMC Cancer",
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TY - JOUR

T1 - Array comparative genomic hybridization analysis discloses chromosome copy number alterations as indicators of patient outcome in lymph node-negative breast cancer

AU - Kikuchi-Koike, Ryoko

AU - Nagasaka, Kazunori

AU - Tsuda, Hitoshi

AU - Ishii, Yasuyuki

AU - Sakamoto, Masaru

AU - Kikuchi, Yoshihiro

AU - Fukui, Shiho

AU - Miyagawa, Yuko

AU - Hiraike, Haruko

AU - Kobayashi, Takayuki

AU - Kinoshita, Takayuki

AU - Kanai, Yae

AU - Shibata, Tatsuhiro

AU - Imoto, Issei

AU - Inazawa, Johji

AU - Matsubara, Osamu

AU - Ayabe, Takuya

PY - 2019/5/30

Y1 - 2019/5/30

N2 - Background: Patients with lymph node metastasis-negative (pN0) invasive breast cancer have favorable outcomes following initial treatment. However, false negatives which occur during routine histologic examination of lymph nodes are reported to underestimate the clinical stage of disease. To identify a high-risk group in pN0 invasive breast cancer, we examined copy number alterations (CNAs) of 800 cancer-related genes. Methods: Using array-based comparative genomic hybridization (CGH) in 51 pN0 cases (19 relapsed and 32 non-relapsed cases), the positivities of specific gene CNAs in the relapsed and non-relapsed groups were compared. An unsupervised hierarchical cluster analysis was then performed to identify case groups that were correlated with patient outcomes. Results: The cluster analysis identified three distinct clusters of cases: groups 1, 2, and 3. The major component was triple-negative cases (69%, 9 of 13) in group 1, luminal B-like (57%, 13 of 23) and HER2-overexpressing (26%, 6 of 23) subtypes in group 2, and luminal A-like subtype (60%, 9 of 15) in group 3. Among all 51 cases, those in group 1 showed significantly worse overall survival (OS) than group 2 (p = 0.014), and 5q15 loss was correlated with worse OS (p = 0.017). Among 19 relapsed cases, both OS and relapse-free survival (RFS) rates were significantly lower in group 1 than in group 2 (p = 0.0083 and 0.0018, respectively), and 5q15 loss, 12p13.31 gain, and absence of 16p13.3 gain were significantly correlated with worse OS and RFS (p = 0.019 and 0.0027, respectively). Conclusions: As the target genes in these loci, NR2F1 (5q15), TNFRSF1A (12p13.31), and ABCA3 (16p13.3) were examined. 5q15 loss, 12p13.31 gain, and absence of 16q13.3 gain were potential indicators of high-risk recurrence and aggressive clinical behavior of pN0 invasive breast cancers.

AB - Background: Patients with lymph node metastasis-negative (pN0) invasive breast cancer have favorable outcomes following initial treatment. However, false negatives which occur during routine histologic examination of lymph nodes are reported to underestimate the clinical stage of disease. To identify a high-risk group in pN0 invasive breast cancer, we examined copy number alterations (CNAs) of 800 cancer-related genes. Methods: Using array-based comparative genomic hybridization (CGH) in 51 pN0 cases (19 relapsed and 32 non-relapsed cases), the positivities of specific gene CNAs in the relapsed and non-relapsed groups were compared. An unsupervised hierarchical cluster analysis was then performed to identify case groups that were correlated with patient outcomes. Results: The cluster analysis identified three distinct clusters of cases: groups 1, 2, and 3. The major component was triple-negative cases (69%, 9 of 13) in group 1, luminal B-like (57%, 13 of 23) and HER2-overexpressing (26%, 6 of 23) subtypes in group 2, and luminal A-like subtype (60%, 9 of 15) in group 3. Among all 51 cases, those in group 1 showed significantly worse overall survival (OS) than group 2 (p = 0.014), and 5q15 loss was correlated with worse OS (p = 0.017). Among 19 relapsed cases, both OS and relapse-free survival (RFS) rates were significantly lower in group 1 than in group 2 (p = 0.0083 and 0.0018, respectively), and 5q15 loss, 12p13.31 gain, and absence of 16p13.3 gain were significantly correlated with worse OS and RFS (p = 0.019 and 0.0027, respectively). Conclusions: As the target genes in these loci, NR2F1 (5q15), TNFRSF1A (12p13.31), and ABCA3 (16p13.3) were examined. 5q15 loss, 12p13.31 gain, and absence of 16q13.3 gain were potential indicators of high-risk recurrence and aggressive clinical behavior of pN0 invasive breast cancers.

KW - ABCA3

KW - Array-CGH

KW - NR2F1

KW - pN0 invasive breast cancer

KW - TNFRSF1A

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U2 - 10.1186/s12885-019-5737-7

DO - 10.1186/s12885-019-5737-7

M3 - Article

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