Science research news Return to previous page
Article Released Fri-24th-October-2014 08:20 GMT
Contact: University of Malaya Institution: University of Malaya
 University Malaya congratulates Prof. Ariffin on their paper in PNAS

In their paper, Prof Ariffin and her collaborators proposed a novel hypothesis that germline TP53 mutation carriers who develop cancer only at a late age may have a form of genetic resistance to early cancer.

Picture 1
Professor Dr. Hany Ariffin
High Impact Research (HIR) is pleased to announce the publication of a paper in the journal, Proceedings of the National Academy of Sciences (PNAS), by Professor Dr. Hany Ariffin from University of Malaya Cancer Research Institute (UMCRI), Faculty of Medicine and her research collaborators.

The paper entitled “Whole genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome” was funded by an HIR MoE Grant and conducted in collaboration with Professor Pierre Hainaut of Institut Albert Bonniot-INSERM, Grenoble and Dr. Chang Chan and Arnold Levine of Institute for Advanced Study, New Jersey.

This study addresses the phenomenon of anticipation seen in families with Li-Fraumeni syndrome (LFS), a cancer predisposition condition defined by germline mutations in the TP53 gene ; the so-called “guardian of the genome”. Previous studies in multi-generational kindreds with LFS have suggested that affected patients develop more rapid cancer onset in successive generations.

It has been proposed that this phenomenon is due to an increased occurance & tolerance of copy number variations with subsequent generations. Prof. Hany’s team analyzed p53 mutations and clinical phenotype in a large database of LFS families as well as performed genome wide sequencing on 13 members of a LFS kindred showing evidence of acceleration in age at cancer onset and increased severity of the syndrome over two generations.

The group manged to address challenging and understudied genetic predisposition mechanisms in an important familial cancer syndrome using a unique sample set and comprehensive sequencing analysis. The findings are supported by both human data as well as p53 knock-out mouse models.

From their findings, Professor Dr. Hany Ariffin and her collaborators have proposed a novel hypothesis that germline TP53 mutation carriers who develop cancer only at a late age may have a form of genetic resistance to early cancer.

They have coined the term "genetic regression" to describe their hypothesis, a new concept in the context of the evolutionary tolerability of germline p53 mutations and provides an alternative view in understanding the phenomenon of anticipation in LFS. It remains to be studied whether other familial syndromes, not just related to cancer, show similar patterns.

Reference:

Ariffin H, et al. Whole genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome. PNAS (Early Edition) accessible at : www.pnas.org/cgi/doi/10.1073/pnas.1417322111

Authors and Affiliations:

Hany Ariffin1,2,, Pierre Hainaut3,4, Anna Puzio-Kuter5, Soo Sin Choong2, Adelyne Sue Li Chan2, Denis Tolkunov5, Gunaretnam Rajagopal5, Wenfeng Kang5, Leon Li Wen Lim1, Shekhar Krishnan1,2 , Kok-Siong Chen1, Maria Isabel Achatz7, Mawar Karsa1, Jannah Shamsani1, Arnold J Levine6 and Chang S Chan5,6

1 University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia
2 Paediatric Haematology-Oncology Unit, University of Malaya Medical Centre, Kuala Lumpur, Malaysia
3 International Prevention Research Institute, Lyon, France
4 Institut Albert Bonniot- INSERM 823, University Grenoble-Alpes, Grenoble, France
5 Rutgers Cancer Institute of New Jersey, New Jersey, USA
6 Institute for Advanced Study, New Jersey, USA
7 Department of Oncogenetics, Hospital AC Camargo, Sao Paulo, Brazil

Keywords associated to this article:
Create Account...