|
Purpose.: Monosomy 3 (M3) and abnormalities of chromosome 8 associate
with poor prognosis in uveal melanomas (UM). Although M3 has been the subject
of more in-depth studies, none have intensively focused on chromosome 8. To
elucidate the potential role of chromosome 8 abnormalities, array comparative
genomic hybridization (aCGH) was performed on primary UM.
Methods.: A
specifically-designed custom high-resolution array was developed focusing on
changes most implicated in UM. Probes for chromosome 8 had a mean spacing of
2.3 kb while chromosomes infrequently affected had a mean spacing of 36.6 kb.
A series of 75 UM, including one formalin-fixed paraffin sample were
analyzed, and where possible control DNA extracted from the patient’s own
peripheral blood was used.
Results.: The most common
copy number abnormalities were chromosome 8 (75%) and M3 (51%), with M3 and
gain of the long arm of chromosome 8 (8q+) associated in 41% of cases. Also
identified were partial deletions of chromosome 3 (3%) and regional 8q+
(23%), and the intensive coverage of chromosome 8 revealed small focal
deletions and amplifications affecting both arms. The most significant
predictor of prognosis was M3/8q+ having a hazard ratio of 10.1 (P
< 0.0001).
Conclusions.: Neither 8p
deletion nor focal changes affecting chromosome 8 were linked to outcome. The
most significant indicator was M3/8q, and multiple 8q+ associated with
shorter survival. Studying UM with this technology provides a powerful robust
tool for predicting prognosis while considering other genetic changes,
allowing the future incorporation of such data as it becomes clinically
significant.
|
