Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer
Authors: Denis Moro-Sibilot
Elisabeth Brambilla
Sylvie Lantuejoul
Christian Brambilla
Arnaud Van Den Broeck
Beatrice Eymin
Sylvie Gazzeri
Journal: Clinical Cancer Research (2008)
Discipline: CLINICAL MEDICINE
Keywords: Epigenetic modifications; histone H4; lung carcinogenesis; acetylated lysines; trimethylated residues
Affiliations: Equipe Bases Moléculaires de la Progression des Cancers du Poumon, Centre de Recherche INSERM U823, Institut Albert Bonniot, Grenoble Cedex, France.

Abstract:  Purpose: Epigenetic modifications of histone have crucial roles in the control of gene activity, nuclear architecture, and genomic stability. In this respect, they may contribute to the development and progression of cancer. We investigated whether epigenetic changes of histone H4 are involved in lung carcinogenesis. Experimental design: Epigenetic modifications of histone H4 were studied by immunohistochemistry in normal lung and 157 lung carcinoma using antibodies specifically recognizing the acetylated (Ac) lysines 5 (K5), K8, K12, K16, and trimethylated (me3) K20 residues of histone H4. Western blotting was used to validate the immunohistochemistry results. H4K20me3 was also studied in 17 preneoplastic lesions. Expression of the Suv4-20h1/2 trimethyltransferases was analyzed by quantitative reverse transcription-PCR in a subset of tumor samples. Results: As compared with normal lung, cancer cells displayed an aberrant pattern of histone H4 modifications with hyperacetylation of H4K5/H4K8, hypoacetylation of H4K12/H4K16, and loss of H4K20 trimethylation. Alteration of H4K20 trimethylation was frequent in squamous cell carcinoma (67%) and was observed in early precursors lesions in which the level of H4K20me3 staining strongly decreased with disease progression. In adenocarcinoma, the down-regulation of H4K20me3 was less frequent (28%) but allowed the identification of a subgroup of stage I adenocarcinoma patients with reduced survival (P = 0.007). Loss of H4K20 trimethylation was associated with decreased expression of Suv4-20h2, a specific H4K20 trimethyltransferase involved in telomere length maintenance. Conclusions: Our findings indicate an important role of histone H4 modifications in bronchial carcinogenesis and highlight H4K20me3 as a candidate biomarker for early detection of and therapeutic approaches to lung cancer. 

Retracted: No

PubPeer comments:
 Figure 3B. Much more similar than you would expect. ![file] , 
 Thank you for your comment. We are considering it seriously. The matter is now under investigation. Information on the outcome and appropriate responses will be posted in the close future. , 
 2020 Editor s Note. https: clincancerres.aacrjournals.org content 26 7 1776 The editors are publishing this note to alert readers to a concern about this article (1). In the actin row of Fig. 3B, there is a missing splice line between samples 12 and 35, and the sets of actin blots in samples 12 and 35 appear to be duplicates. , 
 10.1158 1078-0432.CCR-20-1456 Correction In the original version of this article (1), Saadi Khochbin was mistakenly included in the author list. This error has been corrected in the latest PDF version of the article at the request of Saadi Khochbin and with the agreement of all the authors. The authors regret this error. ,