Lynch syndrome (LS) is a tumor predisposing condition caused by constitutional defects in genes coding for components of the mismatch repair (MMR) apparatus. While hypermethylation of the promoter of the MMR gene MLH1 occurs in about 15% of colorectal cancer samples, it has also been observed as a constitutional alteration, in the absence of DNA sequence mutations, in a small number of LS patients. In order to obtain further insights on the phenotypic characteristics of MLH1 epimutation carriers, we investigated the somatic and constitutional MLH1 methylation status of 14 unrelated subjects with a suspicion of LS who were negative for MMR gene constitutional mutations and whose tumors did not express the MLH1 protein. A novel case of constitutional MLH1 epimutation was identified. This patient was affected with multiple primary tumors, including breast cancer, diagnosed starting from the age of 55 y. Investigation of her offspring by allele specific expression revealed that the epimutation was not stable across generations. We also found MLH1 hypermethylation in cancer samples from 4 additional patients who did not have evidence of constitutional defects. These patients had some characteristics of LS, namely early age at onset and/or positive family history, raising the possibility of genetic influences in the establishment of somatic MLH1 methylation.

MLH1 constitutional and somatic methylation in patients with MLH1 negative tumors fulfilling the revised Bethesda criteria / Crucianelli, Francesca; Tricarico, Rossella; Turchetti, Daniela; Gorelli, Greta; Gensini, Francesca; Sestini, Roberta; Giunti, Laura; Pedroni, Monica; PONZ DE LEON, Maurizio; Civitelli, Serenella; Genuardi, Maurizio. - In: EPIGENETICS. - ISSN 1559-2294. - ELETTRONICO. - 9:10(2014), pp. 1431-1438. [10.4161/15592294.2014.970080]

MLH1 constitutional and somatic methylation in patients with MLH1 negative tumors fulfilling the revised Bethesda criteria

TURCHETTI, Daniela;PEDRONI, Monica;PONZ DE LEON, Maurizio;
2014

Abstract

Lynch syndrome (LS) is a tumor predisposing condition caused by constitutional defects in genes coding for components of the mismatch repair (MMR) apparatus. While hypermethylation of the promoter of the MMR gene MLH1 occurs in about 15% of colorectal cancer samples, it has also been observed as a constitutional alteration, in the absence of DNA sequence mutations, in a small number of LS patients. In order to obtain further insights on the phenotypic characteristics of MLH1 epimutation carriers, we investigated the somatic and constitutional MLH1 methylation status of 14 unrelated subjects with a suspicion of LS who were negative for MMR gene constitutional mutations and whose tumors did not express the MLH1 protein. A novel case of constitutional MLH1 epimutation was identified. This patient was affected with multiple primary tumors, including breast cancer, diagnosed starting from the age of 55 y. Investigation of her offspring by allele specific expression revealed that the epimutation was not stable across generations. We also found MLH1 hypermethylation in cancer samples from 4 additional patients who did not have evidence of constitutional defects. These patients had some characteristics of LS, namely early age at onset and/or positive family history, raising the possibility of genetic influences in the establishment of somatic MLH1 methylation.
2014
9
10
1431
1438
MLH1 constitutional and somatic methylation in patients with MLH1 negative tumors fulfilling the revised Bethesda criteria / Crucianelli, Francesca; Tricarico, Rossella; Turchetti, Daniela; Gorelli, Greta; Gensini, Francesca; Sestini, Roberta; Giunti, Laura; Pedroni, Monica; PONZ DE LEON, Maurizio; Civitelli, Serenella; Genuardi, Maurizio. - In: EPIGENETICS. - ISSN 1559-2294. - ELETTRONICO. - 9:10(2014), pp. 1431-1438. [10.4161/15592294.2014.970080]
Crucianelli, Francesca; Tricarico, Rossella; Turchetti, Daniela; Gorelli, Greta; Gensini, Francesca; Sestini, Roberta; Giunti, Laura; Pedroni, Monica;...espandi
File in questo prodotto:
File Dimensione Formato  
MLH1 constitutional and somatic methylation in patients with MLH1 negative tumors fulfilling the revised Bethesda criteria.pdf

Accesso riservato

Tipologia: Versione pubblicata dall'editore
Dimensione 645.14 kB
Formato Adobe PDF
645.14 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1062803
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 24
social impact