Identification of multiple DNA copy number alterations including frequent 8p11.22 amplification in conjunctival squamous cell carcinoma.

Authors: Asnaghi, Laura  Alkatan, Hind  Mahale, Alka  Othman, Maha  Alwadani, Saeed  Al-Hussain, Hailah  Jastaneiah, Sabah  Yu, Wayne  Maktabi, Azza  Edward, Deepak P  Eberhart, Charles G 
Citation: Asnaghi L, etal., Invest Ophthalmol Vis Sci. 2014 Dec 9;55(12):8604-13. doi: 10.1167/iovs.14-14920.
Pubmed: (View Article at PubMed) PMID:25491297
DOI: Full-text: DOI:10.1167/iovs.14-14920


PURPOSE: Little is known about the molecular alterations that drive formation and growth of conjunctival squamous cell carcinoma (cSCC). We therefore sought to identify genetic changes that could be used as diagnostic markers or therapeutic targets.
METHODS: The DNA extracted from 10 snap-frozen cSCC tumor specimens and 2 in situ carcinomas was analyzed using array-based comparative genomic hybridization (aCGH), and further examined with NanoString and quantitative PCR.
RESULTS: The number of regions of DNA loss ranged from 1 to 23 per tumor, whereas gains and amplifications ranged from 1 to 15 per tumor. Most large regions of chromosomal gain and loss were confirmed by NanoString karyotype analysis. The commonest alteration was amplification of 8p11.22 in 9 tumors (75%), and quantitative PCR analysis revealed 100-fold or greater overexpression of ADAM3A mRNA from 8p11.22 locus. In addition, recurring losses were observed at 14q13.2 and 22q11.23, both lost in 5 (42%) of the 12 tumors, and at 12p13.31, lost in 4 (33%) of the 12 samples. Of the eight loci associated with the DNA damage repair syndrome xeroderma pigmentosum, three showed loss of at least one allele in our aCGH analysis, including XPA (9q22.33, one tumor), XPE/DDB2 (11p11.2, one tumor) and XPG/ERCC5 (13q33.1, three tumors).
CONCLUSIONS: Conjunctival SCC contains a range of chromosomal alterations potentially important in tumor formation and growth. Amplification of 8p11.22 and overexpression of ADAM3A suggests a potential role for this protease. Our findings also suggest that defects in DNA repair loci are important in sporadic cSCC.

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CRRD ID: 13831354
Created: 2019-01-07
Species: All species
Last Modified: 2019-01-07
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.