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 | |
| Publication status | Published - Jul 9 2019 |
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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
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TY - JOUR
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
C2 - 31288858
VL - 11
SP - 100
JO - Clinical Epigenetics
JF - Clinical Epigenetics
SN - 1868-7075
IS - 1
ER -