Lack of oncogenic GNAQ mutations in melanocytic lesions of the conjunctiva as compared to uveal melanoma.
OBJECTIVE
Somatic mutations in codon 209 of the GNAQ gene are the first initiating events to be identified in uveal melanoma. The purpose of this study was to search for GNAQ209 mutations in conjunctival melanocytic lesions.


METHODS
Forty archival samples of conjunctival melanocytic lesions (conjunctival nevi, primary acquired melanosis, and conjunctival melanoma), 27 samples of uveal melanoma, and 11 samples of uveal melanoma metastases to the liver (3 of which matched primary uveal melanoma samples)-a total of 78 samples from 75 patients- were examined for the presence of GNAQ209 mutations by using chip-based, matrix-assisted laser-desorption time-of-flight (MALDI-TOF) mass spectrometry. Direct sequencing was also performed.


RESULTS
The GNAQ209 mutation was identified in 12 (44.5%) uveal melanoma samples and 4 (36.5%) of the 11 metastases of uveal melanoma. It was not detected in any of the other melanocytic lesions.


CONCLUSIONS
The GNAQ209 mutation rate in uveal melanoma in this study is in line with the rate in other reports. The finding of the same genotype in the primary tumors and their metastases suggests that mutation in GNAQ is an early event in uveal melanoma tumorigenesis. The lack of GNAQ mutations in conjunctival melanocytic lesions suggests the involvement of a different tumorigenic pathway from that of uveal melanoma.
Dratviman-Storobinsky
Olga
O
The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petah Tiqwa, Israel.
Cohen
Yoram
Y
Frenkel
Shahar
S
Pe'er
Jacob
J
Goldenberg-Cohen
Nitza
N
D003230:Conjunctival Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008548:Melanosis / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009508:Nevus, Pigmented / Q000235:genetics* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D004273:DNA, Neoplasm; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D015513:Oncogene Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11