IOVS Journal of Clinical Investigation
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(Investigative Ophthalmology and Visual Science. 2007;48:4919-4923.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-0061
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Expression of APITD1 Is Not Related to Copy Number Changes of Chromosomal Region 1p36 or the Prognosis of Uveal Melanoma

Walter van Gils,1,2 Hanneke W. Mensink,3 Emine Kilic,1,2 Jolanda Vaarwater,3 Michael M. Verbiest,1 Dion Paridaens,3 Gregorius P. Luyten,2,4 Annelies de Klein,1 and Hennie T. Brüggenwirth1

1From the Departments of Clinical Genetics and 2Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands; the 3Rotterdam Eye Hospital, Rotterdam, The Netherlands; and the 4Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.

PURPOSE. Concurrent loss of chromosome arm 1p, region 36, and chromosome 3 leads to decreased disease-free survival in patients with uveal melanoma. A candidate tumor-suppressor gene APITD1 is located on the critical region on chromosome arm 1p, and it was therefore hypothesized that lower expression levels of this gene could lead to decreased survival in patients, with concurrent loss of a region on chromosome arm 1p and chromosome 3. Using neuroblastoma cells, which, like uveal melanoma, originate from neural crest cells, a former study showed that APITD1 has cell growth and/or cell death properties. In this study, APITD1 expression was analyzed to determine whether it corresponds with the DNA copy number and is related to survival in uveal melanoma.

METHODS. To detect whether loss in the copy number of APITD1 results in lowered mRNA expression of the gene, FISH analysis was combined with real-time PCR. In addition, the effect of APITD1 expression on survival was studied by using Kaplan-Meier survival analysis.

RESULTS. Expression of APITD1 mRNA was not related to DNA copy number (P = 0.956) or chromosome 3 status (P = 0.958). Kaplan-Meier survival analysis showed very similar survival curves for tumors with high and low APITD1 expression, with a log-rank significance value of P = 0.9682.

CONCLUSIONS. These results indicate that APITD1 is not the tumor suppressor gene on 1p36 responsible for the negative prognostic effect in uveal melanoma with concurrent loss of chromosome arm 1p, region 36, and chromosome 3.






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