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Two gene mutations linked to hardest-to-beat ovarian cancer

13 September 2010

By Dr Lux Fatimathas

Appeared in BioNews 575

Two new genetic mutations associated with the aggressive cancer, ovarianclear cell carcinoma, have been identified by two independent studies. The mutations - in genes ARID1A and PPP2R1A - shed light on how clear cell tumours may arise and potentially provide potential new drug targets.

'They [the mutations] may provide opportunities for developing new biomarkers and therapies that target those genes', says Dr Nickolas Papadopoulos of Johns Hopkins University, Baltimore who was involved in one of the studies, published this month in Science Express.

Dr Papadoulos and his colleagues found mutations in the gene PPP2R1A 7.1 per cent of ovarian clear cell carcinoma samples and mutations in ARID1A in 57 per cent of samples.

'The frequency of these ARID1A mutations in the ovarian tumour samples drew our attention because the gene is involved in determining the epigenetics of cells', says Dr Bert Vogelstein who led the study at John Hopkins University, Baltimore.

Changes in the epigenetics of a cell are known to occur in cancers. One method by which gene expression can be altered epigenetically is through the packaging of DNA into tighter bundles called chromatin. ARID1A is known to be involved in chromatin re-modelling.

'The mutations in ARID1A provide an important new link between genetic and epigenetic mechanisms in human cancer and may help identify epigenetic changes that can be targeted with therapies', says Dr Victor Velculescu of Johns Hopkins University, Baltimore who was involved in the study.

A second study published in the New England Journal of Medicine supported the findings at Johns Hopkins University.

'ARID1A mutations were identified in 55 of 119 (46 per cent) ovarian clear-cell carcinomas [and] 10 of the 33 (30 per cent) endometrioid carcinomas,' wrote authors of the study led by Dr David Huntsman of the British Columbia Cancer Agency, Vancouver.

Dr Huntsman and colleagues conclude that mutations in ARID1A play a 'critical role... in the genesis of a substantial fraction of ovarian clear-cell and endometriod carcinomas'.

'If the disruption of ARID1A drives cancer by inappropriately activating some other pathway, then that pathway could, in principle, be targeted. That's one of the issues that's going to be very important to address as we move forward', says Dr Vogelstein.

Ovarian clear cell carcinoma is responsible for approximately 10 per cent of all ovarian cancers, but does not respond to chemotherapy making it difficult to treat. 

 

SOURCES & REFERENCES
2 Genes Have Possible Link to Deadly Ovarian Cancer
BusinessWeek | 08 September 2010
 
New England Journal of Medicine | 08 September 2010
 
Science Express | 08 September 2010
 
GEN | 09 September 2010
 
Howard Hughes Medical Institute | 08 September 2010
 
Reuters | 09 September 2010
 

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