Clustered protocadherins methylation alterations in cancer

Ana Florencia Vega-Benedetti, Eleonora Loi, Loredana Moi, Sylvain Blois, Antonio Fadda, Manila Antonelli, Antonella Arcella, Manuela Badiali, Felice Giangaspero, Isabella Morra, Amedeo Columbano, Angelo Restivo, Luigi Zorcolo, Viviana Gismondi, Liliana Varesco, Sara Erika Bellomo, Silvia Giordano, Matteo Canale, Andrea Casadei-Gardini, Luca FaloppiMarco Puzzoni, Mario Scartozzi, Pina Ziranu, Giuseppina Cabras, Pierluigi Cocco, Maria Grazia Ennas, Giannina Satta, Mariagrazia Zucca, Daniele Canzio, Patrizia Zavattari

Research output: Contribution to journalArticle

Abstract

Background: Clustered protocadherins (PCDHs) map in tandem at human chromosome 5q31 and comprise three multi-genes clusters: α-, β- and γ-PCDH. The expression of this cluster consists of a complex mechanism involving DNA hub formation through DNA-CCTC binding factor (CTCF) interaction. Methylation alterations can affect this interaction, leading to transcriptional dysregulation. In cancer, clustered PCDHs undergo a mechanism of long-range epigenetic silencing by hypermethylation. Results: In this study, we detected frequent methylation alterations at CpG islands associated to these clustered PCDHs in all the solid tumours analysed (colorectal, gastric and biliary tract cancers, pilocytic astrocytoma), but not hematologic neoplasms such as chronic lymphocytic leukemia. Importantly, several altered CpG islands were associated with CTCF binding sites. Interestingly, our analysis revealed a hypomethylation event in pilocytic astrocytoma, suggesting that in neuronal tissue, where PCDHs are highly expressed, these genes become hypomethylated in this type of cancer. On the other hand, in tissues where PCDHs are lowly expressed, these CpG islands are targeted by DNA methylation. In fact, PCDH-associated CpG islands resulted hypermethylated in gastrointestinal tumours. Conclusions: Our study highlighted a strong alteration of the clustered PCDHs methylation pattern in the analysed solid cancers and suggested these methylation aberrations in the CpG islands associated with PCDH genes as powerful diagnostic biomarkers.

Original languageEnglish
Article number100
JournalClinical Epigenetics
Volume11
Issue number1
DOIs
Publication statusPublished - Jul 9 2019

Fingerprint

CpG Islands
Methylation
Astrocytoma
Neoplasms
Biliary Tract Neoplasms
DNA
Human Chromosomes
Hematologic Neoplasms
DNA Methylation
B-Cell Chronic Lymphocytic Leukemia
Multigene Family
Epigenomics
Genes
Colorectal Neoplasms
Stomach
Biomarkers
Binding Sites

Keywords

  • Biliary tract cancer
  • BTC
  • Cancer methylation alteration
  • Chronic lymphocytic leukemia
  • CLL
  • Clustered PCDH
  • Colorectal adenoma
  • Colorectal carcinoma
  • CpG islands
  • CRA
  • CRC
  • CTCF
  • Gastric cancer
  • GC
  • LGG
  • Low grade glioma
  • PA
  • Pilocytic astrocytoma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

Cite this

Vega-Benedetti, A. F., Loi, E., Moi, L., Blois, S., Fadda, A., Antonelli, M., ... Zavattari, P. (2019). Clustered protocadherins methylation alterations in cancer. Clinical Epigenetics, 11(1), [100]. https://doi.org/10.1186/s13148-019-0695-0

Clustered protocadherins methylation alterations in cancer. / Vega-Benedetti, Ana Florencia; Loi, Eleonora; Moi, Loredana; Blois, Sylvain; Fadda, Antonio; Antonelli, Manila; Arcella, Antonella; Badiali, Manuela; Giangaspero, Felice; Morra, Isabella; Columbano, Amedeo; Restivo, Angelo; Zorcolo, Luigi; Gismondi, Viviana; Varesco, Liliana; Bellomo, Sara Erika; Giordano, Silvia; Canale, Matteo; Casadei-Gardini, Andrea; Faloppi, Luca; Puzzoni, Marco; Scartozzi, Mario; Ziranu, Pina; Cabras, Giuseppina; Cocco, Pierluigi; Ennas, Maria Grazia; Satta, Giannina; Zucca, Mariagrazia; Canzio, Daniele; Zavattari, Patrizia.

In: Clinical Epigenetics, Vol. 11, No. 1, 100, 09.07.2019.

Research output: Contribution to journalArticle

Vega-Benedetti, AF, Loi, E, Moi, L, Blois, S, Fadda, A, Antonelli, M, Arcella, A, Badiali, M, Giangaspero, F, Morra, I, Columbano, A, Restivo, A, Zorcolo, L, Gismondi, V, Varesco, L, Bellomo, SE, Giordano, S, Canale, M, Casadei-Gardini, A, Faloppi, L, Puzzoni, M, Scartozzi, M, Ziranu, P, Cabras, G, Cocco, P, Ennas, MG, Satta, G, Zucca, M, Canzio, D & Zavattari, P 2019, 'Clustered protocadherins methylation alterations in cancer', Clinical Epigenetics, vol. 11, no. 1, 100. https://doi.org/10.1186/s13148-019-0695-0
Vega-Benedetti AF, Loi E, Moi L, Blois S, Fadda A, Antonelli M et al. Clustered protocadherins methylation alterations in cancer. Clinical Epigenetics. 2019 Jul 9;11(1). 100. https://doi.org/10.1186/s13148-019-0695-0
Vega-Benedetti, Ana Florencia ; Loi, Eleonora ; Moi, Loredana ; Blois, Sylvain ; Fadda, Antonio ; Antonelli, Manila ; Arcella, Antonella ; Badiali, Manuela ; Giangaspero, Felice ; Morra, Isabella ; Columbano, Amedeo ; Restivo, Angelo ; Zorcolo, Luigi ; Gismondi, Viviana ; Varesco, Liliana ; Bellomo, Sara Erika ; Giordano, Silvia ; Canale, Matteo ; Casadei-Gardini, Andrea ; Faloppi, Luca ; Puzzoni, Marco ; Scartozzi, Mario ; Ziranu, Pina ; Cabras, Giuseppina ; Cocco, Pierluigi ; Ennas, Maria Grazia ; Satta, Giannina ; Zucca, Mariagrazia ; Canzio, Daniele ; Zavattari, Patrizia. / Clustered protocadherins methylation alterations in cancer. In: Clinical Epigenetics. 2019 ; Vol. 11, No. 1.
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abstract = "Background: Clustered protocadherins (PCDHs) map in tandem at human chromosome 5q31 and comprise three multi-genes clusters: α-, β- and γ-PCDH. The expression of this cluster consists of a complex mechanism involving DNA hub formation through DNA-CCTC binding factor (CTCF) interaction. Methylation alterations can affect this interaction, leading to transcriptional dysregulation. In cancer, clustered PCDHs undergo a mechanism of long-range epigenetic silencing by hypermethylation. Results: In this study, we detected frequent methylation alterations at CpG islands associated to these clustered PCDHs in all the solid tumours analysed (colorectal, gastric and biliary tract cancers, pilocytic astrocytoma), but not hematologic neoplasms such as chronic lymphocytic leukemia. Importantly, several altered CpG islands were associated with CTCF binding sites. Interestingly, our analysis revealed a hypomethylation event in pilocytic astrocytoma, suggesting that in neuronal tissue, where PCDHs are highly expressed, these genes become hypomethylated in this type of cancer. On the other hand, in tissues where PCDHs are lowly expressed, these CpG islands are targeted by DNA methylation. In fact, PCDH-associated CpG islands resulted hypermethylated in gastrointestinal tumours. Conclusions: Our study highlighted a strong alteration of the clustered PCDHs methylation pattern in the analysed solid cancers and suggested these methylation aberrations in the CpG islands associated with PCDH genes as powerful diagnostic biomarkers.",
keywords = "Biliary tract cancer, BTC, Cancer methylation alteration, Chronic lymphocytic leukemia, CLL, Clustered PCDH, Colorectal adenoma, Colorectal carcinoma, CpG islands, CRA, CRC, CTCF, Gastric cancer, GC, LGG, Low grade glioma, PA, Pilocytic astrocytoma",
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T1 - Clustered protocadherins methylation alterations in cancer

AU - Vega-Benedetti, Ana Florencia

AU - Loi, Eleonora

AU - Moi, Loredana

AU - Blois, Sylvain

AU - Fadda, Antonio

AU - Antonelli, Manila

AU - Arcella, Antonella

AU - Badiali, Manuela

AU - Giangaspero, Felice

AU - Morra, Isabella

AU - Columbano, Amedeo

AU - Restivo, Angelo

AU - Zorcolo, Luigi

AU - Gismondi, Viviana

AU - Varesco, Liliana

AU - Bellomo, Sara Erika

AU - Giordano, Silvia

AU - Canale, Matteo

AU - Casadei-Gardini, Andrea

AU - Faloppi, Luca

AU - Puzzoni, Marco

AU - Scartozzi, Mario

AU - Ziranu, Pina

AU - Cabras, Giuseppina

AU - Cocco, Pierluigi

AU - Ennas, Maria Grazia

AU - Satta, Giannina

AU - Zucca, Mariagrazia

AU - Canzio, Daniele

AU - Zavattari, Patrizia

PY - 2019/7/9

Y1 - 2019/7/9

N2 - Background: Clustered protocadherins (PCDHs) map in tandem at human chromosome 5q31 and comprise three multi-genes clusters: α-, β- and γ-PCDH. The expression of this cluster consists of a complex mechanism involving DNA hub formation through DNA-CCTC binding factor (CTCF) interaction. Methylation alterations can affect this interaction, leading to transcriptional dysregulation. In cancer, clustered PCDHs undergo a mechanism of long-range epigenetic silencing by hypermethylation. Results: In this study, we detected frequent methylation alterations at CpG islands associated to these clustered PCDHs in all the solid tumours analysed (colorectal, gastric and biliary tract cancers, pilocytic astrocytoma), but not hematologic neoplasms such as chronic lymphocytic leukemia. Importantly, several altered CpG islands were associated with CTCF binding sites. Interestingly, our analysis revealed a hypomethylation event in pilocytic astrocytoma, suggesting that in neuronal tissue, where PCDHs are highly expressed, these genes become hypomethylated in this type of cancer. On the other hand, in tissues where PCDHs are lowly expressed, these CpG islands are targeted by DNA methylation. In fact, PCDH-associated CpG islands resulted hypermethylated in gastrointestinal tumours. Conclusions: Our study highlighted a strong alteration of the clustered PCDHs methylation pattern in the analysed solid cancers and suggested these methylation aberrations in the CpG islands associated with PCDH genes as powerful diagnostic biomarkers.

AB - Background: Clustered protocadherins (PCDHs) map in tandem at human chromosome 5q31 and comprise three multi-genes clusters: α-, β- and γ-PCDH. The expression of this cluster consists of a complex mechanism involving DNA hub formation through DNA-CCTC binding factor (CTCF) interaction. Methylation alterations can affect this interaction, leading to transcriptional dysregulation. In cancer, clustered PCDHs undergo a mechanism of long-range epigenetic silencing by hypermethylation. Results: In this study, we detected frequent methylation alterations at CpG islands associated to these clustered PCDHs in all the solid tumours analysed (colorectal, gastric and biliary tract cancers, pilocytic astrocytoma), but not hematologic neoplasms such as chronic lymphocytic leukemia. Importantly, several altered CpG islands were associated with CTCF binding sites. Interestingly, our analysis revealed a hypomethylation event in pilocytic astrocytoma, suggesting that in neuronal tissue, where PCDHs are highly expressed, these genes become hypomethylated in this type of cancer. On the other hand, in tissues where PCDHs are lowly expressed, these CpG islands are targeted by DNA methylation. In fact, PCDH-associated CpG islands resulted hypermethylated in gastrointestinal tumours. Conclusions: Our study highlighted a strong alteration of the clustered PCDHs methylation pattern in the analysed solid cancers and suggested these methylation aberrations in the CpG islands associated with PCDH genes as powerful diagnostic biomarkers.

KW - Biliary tract cancer

KW - BTC

KW - Cancer methylation alteration

KW - Chronic lymphocytic leukemia

KW - CLL

KW - Clustered PCDH

KW - Colorectal adenoma

KW - Colorectal carcinoma

KW - CpG islands

KW - CRA

KW - CRC

KW - CTCF

KW - Gastric cancer

KW - GC

KW - LGG

KW - Low grade glioma

KW - PA

KW - Pilocytic astrocytoma

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DO - 10.1186/s13148-019-0695-0

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