Frequency, molecular pathology and potential clinical significance of partial chromosome 3 aberrations in uveal melanoma.
Frequency, molecular pathology and potential clinical significance of partial chromosome 3 aberrations in uveal melanoma.
复制标题
DOI：
10.1038/modpathol.2011.51
复制
发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Davidorf FH
中科院分区：
文献类型：
--
作者：
Abdel-Rahman MH;Christopher BN;Faramawi MF;Said-Ahmed K;Cole C;McFaddin A;Ray-Chaudhury A;Heerema N;Davidorf FH
葡萄膜黑色素瘤中3号染色体部分改变的临床意义尚不清楚。此外，在已发表的文献中，报道的频率差异很大，从0到48%。以下研究的目的是确定葡萄膜黑色素瘤中3号染色体部分改变的频率、分子病理学和潜在的临床意义。我们研究了47例葡萄膜黑色素瘤，平均随访时间为36个月。在这些人中，有14人确认有转移。利用3号染色体上的微卫星标记研究了等位基因不平衡/杂合性丢失，这些标记位于先前报道的最小缺失重叠区域。通过常规细胞遗传学或比较基因组杂交(CGH)对部分患者的染色体改变进行评估。利用基因分型技术，在47个肿瘤中有14个(30%)检测到3号染色体部分改变。在23例细胞遗传学/CGH正常的肿瘤中，8/23(38%)发现3号染色体的部分改变，这是由3号染色体的获得(4/8)和丢失(4/8)共同引起的，细胞遗传学检测到3号染色体复杂异常的频率很高。在14例确诊有转移的肿瘤中，仅1例3号染色体部分改变，其余为3号单体。将侵袭性疾病标志物限制为3号单体，基因分型对检测侵袭性葡萄膜黑色素瘤的敏感性为93%，特异性为67%。总之，3号染色体的部分改变在葡萄膜黑色素瘤中很常见，主要是由于复杂的细胞遗传学改变导致3号染色体的部分增加和/或部分丢失。3号染色体的部分改变不太可能与治疗后3年内转移的高度侵袭性葡萄膜黑色素瘤有关。基于微卫星的3号染色体基因分型对检测侵袭性葡萄膜黑色素瘤高度敏感。
The clinical significance of partial chromosome 3 alteration in uveal melanoma is still not clear. Also, the reported frequencies vary considerably in the published literature from 0 to 48%. The aims of the following study were to identify the frequency, molecular pathology and potential clinical significance of partial chromosome 3 alteration in uveal melanoma. We studied 47 uveal melanomas with an average follow-up of 36 months. Of these, 14 had confirmed metastasis. Allelic imbalance/loss of heterozygosity was studied using microsatellite markers on chromosome 3 enriched in markers located in the previously reported smallest regions of deletion overlap. Chromosomal alterations were assessed by conventional cytogenetics or comparative genomic hybridization (CGH) in a subset of patients. Utilizing genotyping, partial chromosome 3 alteration was detected in 14/47 tumors (30%). In the 23 tumors with available cytogenetic/CGH, partial chromosome 3 alteration was detected in 8/23 (38%) and was caused by both gains (4/8) and losses (4/8) of chromosome 3 with high frequency of complex chromosome 3 aberrations detected by cytogenetics. Out of the 14 tumors with confirmed metastasis, only 1 showed partial chromosome 3 alteration and the remaining showed monosomy 3. By limiting the aggressive disease marker to monosomy 3, genotyping showed 93% sensitivity and 67% specificity for detection of aggressive uveal melanoma. In conclusion, partial chromosome 3 alterations are common in uveal melanoma and mostly caused by complex cytogenetic changes leading to partial gains and/or partial losses of chromosome 3. Partial chromosome 3 alteration is not likely to be associated with highly aggressive uveal melanoma that metastasizes within the first 3 years after treatment. Microsatellite-based genotyping of chromosome 3 is highly sensitive for detection of aggressive uveal melanoma.
登录
查看更多内容
影响因子：
8.8
作者：
Hughes, S;Damato, BE;Houlston, RS
通讯作者：
Houlston, RS
影响因子：
--
作者：
Damato, Bertil;Coupland, Sarah E.
通讯作者：
Coupland, Sarah E.
影响因子：
4.4
作者：
Damato, Bertil;Dopierala, Justyna;Coupland, Sarah E.
通讯作者：
Coupland, Sarah E.
影响因子：
4.4
作者：
Mensink, Hanneke W.;Vaarwater, Jolanda;de Klein, Annelies
通讯作者：
de Klein, Annelies
影响因子：
3.9
作者：
Cross, NA;Ganesh, A;Sisley, K
通讯作者：
Sisley, K