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Exome Sequencing Reveals the Likely Involvement of SOX10 in Uveal Melanoma

Das, Debodipta*; Kaur, Inderjeet; Ali, Mohammad Javed; Biswas, Nidhan K.; Das, Subrata§; Kumar, Shantanu*; Honavar, Santosh G.; Maitra, Arindam; Chakrabarti, Subhabrata; Majumder, Partha P.

doi: 10.1097/OPX.0000000000000309

Purpose To identify the spectrum of somatic mutations in an Asian Indian patient with uveal melanoma (UM) without metastasis using exome sequencing.

Case Report A 49-year-old man from India was diagnosed as having cilio-choroidal (uveal) melanoma (UM), without metastasis, in his right eye with the help of magnetic resonance imaging. This was later confirmed by histopathological evaluation. Two individuals from India with non-neoplastic blind eyes were recruited as controls. The affected eyes from the UM patient and the two control individuals were enucleated, and uveal tissues were collected. DNA was extracted from uveal tissue, and the matched blood sample from each of the three individuals was followed by exome sequencing. Statistical and bioinformatic analyses were done to identify somatic mutations and their putative associations with UM. Thirty-one somatic mutations (25 amino acid altering) in protein-coding (exonic) regions were detected in the UM patient. Of the amino acid–altering somatic mutations, 16 mutations were predicted to be candidate mutations relevant to UM. Somatic mutations, putatively causal for UM, were identified in GNAQ, SF3B1, and SOX10.

Conclusions Somatic mutations in GNAQ and SF3B1 genes were probable drivers of UM in the Indian patient; these were also reported earlier in some White patients. In addition, a frameshift deletion of 20 base pairs has been identified in SOX10 in the UM patient. Somatic mutations in SOX10, a transcription factor, which acts upstream of microphthalmia-associated transcription factor and synergizes with microphthalmia-associated transcription factor, was identified in some melanoma cell lines. The transcription factor SOX10 was found to have an essential role in melanocyte development and pigmentation. Our finding of the frameshift deletion (p.H387fs) in exon 4 of SOX10 in UM provides an important insight and complements earlier findings of mutations in GNAQ and SF3B1 on the genomic basis of UM.





National Institute of Biomedical Genomics, Kalyani, India (DD, NKB, SD, SK, AM, PPM); Prof. Brien Holden Eye Research Centre (IK, SC), and Department of Orbits and Ocular Oncology (MJA, SGH), LV Prasad Eye Institute, Hyderabad, India.

Partha P. Majumder National Institute of Biomedical Genomics Netaji Subhas Sanatorium (TB Hospital) 2nd Floor PO: NSS Kalyani 741251 West Bengal, India e-mail:

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© 2014 American Academy of Optometry