Keywords: PIK3CA,
ARID1A, PPP2R1A,
KRAS. | Exomic analysis of the genetics of ovarian clear cell carcinoma.
This week's story by Helen Gavaghan. |
The paper describes exomic genetic work on ovarian clear cell carcinoma. Exomics homes in on specific patients, protein coding regions of the genome and is aimed at elucidating specific disease states.
After purification by immunoaffinity precipitation of the cancer cells from tumours from eight patients the exomes of the tumours were sequenced and compared with those from normal cells taken from the same patients. Of the four mutated genes which appeared in at least two of the eight patients not one of them appeared in all of the patients. The four genes were: KRAS, known, write the authors, to code for a well known oncoprotein - and they give no details of the KRAS protein function or associations - and PIK3CA (which codes for a kinase subunit), PPP2R1A (from its sequence, probably, write the authors, an oncogene, and ARID1A having the hall marks of a tumour suppressor. PPP2R1A codes for a regulatory subunit of a phosphatase. ARID1A codes for an AT rich domain containing a protein that participates in chromatin remodeling.
PPP2R1A and ARID1A were novel in databases such as the Catalogue of somatic mutations in cancer.
DISCOVERY
One patient aged 58 with a 1C stage tumour had only ARID1A expressed (correct).
Three patients had both ARID1A and PIK3CA expressed; patient 1 age 39, stage IV; patient 2 age 47, stage IIIC; and patient 8 age 53, stage IC (correct).
One patient, patient 6 aged 46 with a recurrent tumour (data on tumour stage not available) had only PIK3CA expressed (correct).
Patient 5 had PPP2R1A and KRAS expressed. She was aged 55 with a stage IC tumour (correct).
And patient 7, aged 52 with a stage IIIC tumour had ARID1A and PPP2R1A expressed (correct).
Patient 4 aged 32 with a stage IV tumour had only KRAS expressed of the four genes identified as being in more than two tumours among the discovery patient group.
VALIDATION
Having identified and characterised expression of PIK3CA, PPP2R1, KRAS and ARID1A in eight patients the researchers next sequenced the genes in 34 additional patients for validation and noticed PIK3CA mutations in 40 per cent of the 42 tumours, 4.7 per cent KRAS mutations, 7.1 per cent PPP2R1A and 57 Per cent ARID1A.
In seven OCCC cell lines other than the 42 for discovery and validation five cell lines had ARID1A mutations, three had PPP2R1A and one had KRAS and four had PIK3CA.
For the discovery screen the data give the sample id, transcript accession, gene sequence, the cDNA, the protein and the type of mutation for all the mutated genes noted including the four highlighted in the paper which appeared in more than one of the 8 tumours selected for discovery.
Based on a paper in Science Express. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma by S Jones et al. Published 5pm EDT 8.8.10 to coincide with publication in the New England Journal of Medicine. 10.1126/science.1196333.
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