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Molecular Cancer
Published in: Molecular Cancer 1/2009

Open Access 01-12-2009 | Research

The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias

Authors: Luke B Hesson, Thomas L Dunwell, Wendy N Cooper, Daniel Catchpoole, Anna T Brini, Raffaella Chiaramonte, Mike Griffiths, Andrew D Chalmers, Eamonn R Maher, Farida Latif

Published in: Molecular Cancer | Issue 1/2009

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Abstract

Background

The Ras-assocation family (RASSF) of tumour suppressor genes (TSGs) contains 10 members that encode proteins containing Ras-assocation (RA) domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1–10 in a series of childhood acute lymphocytic leukaemias (ALL) and normal blood and bone marrow samples.

Results

COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51) B-ALL and 41% (12/29) T-ALL, whilst RASSF10 was methylated in 16% (8/51) B-ALL and 88% (23/26) T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC).

Conclusion

This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia.
Appendix
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Metadata
Title
The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias
Authors
Luke B Hesson
Thomas L Dunwell
Wendy N Cooper
Daniel Catchpoole
Anna T Brini
Raffaella Chiaramonte
Mike Griffiths
Andrew D Chalmers
Eamonn R Maher
Farida Latif
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2009
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-8-42

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