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 Faloppi; Marco Puzzoni; Mario Scartozzi; Pina Ziranu; Giuseppina Cabras; Pierluigi Cocco; Maria Grazia Ennas; Giannina Satta; Mariagrazia Zucca; Daniele Canzio; Patrizia Zavattari

doi:10.1186/s13148-019-0695-0

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

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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.

Original language	English
Pages (from-to)	100
Journal	Clinical Epigenetics
Volume	11
Issue number	1
DOIs	https://doi.org/10.1186/s13148-019-0695-0
Publication status	Published - Jul 9 2019

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Vega-Benedetti, A. F., 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, S. E., Giordano, S., Canale, M., Casadei-Gardini, A., ... 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, 09.07.2019, p. 100.

Research output: Contribution to journal › Article › peer-review

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, pp. 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. pp. 100.

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title = "Clustered protocadherins methylation alterations in cancer",

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.",

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

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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.

U2 - 10.1186/s13148-019-0695-0

DO - 10.1186/s13148-019-0695-0

M3 - Article

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JO - Clinical Epigenetics

JF - Clinical Epigenetics

SN - 1868-7075

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