Raghavan Ravi, Balani Jyoti, Perry Arie, Margraf Linda, Vono Mary B, Cai Dan X, Wyatt Robert E, Rushing Elisabeth J, Bowers Daniel C, Hynan Linda S, White Charles L
Neuropathology Laboratory, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9073, USA.
J Neuropathol Exp Neurol. 2003 May;62(5):530-7. doi: 10.1093/jnen/62.5.530.
Oligodendrogliomas (OGs) are rare in children and have not been well characterized from a molecular viewpoint. In adults, losses on chromosomes 1p and/or 19q are common in "oligodendroglial" neoplasms and are highly associated with chemosensitivity and greater length of survival, especially in the anaplastic category. We have analyzed the 1p/19q status of pediatric OGs and compared it with similar alterations in adult OGs. Paraffin sections from 26 pediatric OGs (21 WHO Grade II OGs: 2 anaplastic oligodendrogliomas [AOGs]: and 3 mixed oligo-astrocytomas [MOA]) were retrieved. Fluorescence in situ hybridization (FISH) was performed using probes spanning the 1p32 and 19q13 regions. In tumors from children 0 to 9 years of age (n = 15), none had any deletions on 1p or 19q, but 2 had polysomies for 1p and/or 19q. All are alive and 4 have had recurrences. In tumors from children > 9 years, losses were identified on chromosomes 1p (5/11; 45%) and/or 19q (3/11; 27%), but to a much lesser extent than that observed in adult OGs. Tumors from 6 older patients also had polysomies for 1p and/or 19q. Although the majority of the older children are alive, 4 had recurrences. Curiously, 2 of the older children with AOGs had combined losses and polysomies on 1p and 19q, but responded poorly to treatment and died within a year. We conclude that alterations on 1p or 19q are infrequent in pediatric compared to adult OGs and are virtually absent in OGs presenting in the first decade of life. Compared to adults therefore, different genetic pathways are likely involved in the pathogenesis of most pediatric OGs. Genomic screening on a larger series is clearly indicated to delineate the unique molecular characteristics of these rare pediatric tumors.
少突胶质细胞瘤(OGs)在儿童中较为罕见,从分子角度尚未得到充分的特征描述。在成人中,1号染色体短臂(1p)和/或19号染色体长臂(19q)缺失在“少突胶质细胞”肿瘤中很常见,并且与化疗敏感性和更长的生存期高度相关,尤其是在间变性类型中。我们分析了儿童OGs的1p/19q状态,并将其与成人OGs中的类似改变进行了比较。检索了26例儿童OGs(21例世界卫生组织二级OGs:2例间变性少突胶质细胞瘤[AOGs];3例少突-星形细胞瘤[MOA])的石蜡切片。使用跨越1p32和19q13区域的探针进行荧光原位杂交(FISH)。在0至9岁儿童的肿瘤(n = 15)中,没有一个在1p或19q上有任何缺失,但有2个在1p和/或19q上有多体性。所有患者均存活,4例复发。在9岁以上儿童的肿瘤中,在1号染色体短臂(1p)(5/11;45%)和/或19号染色体长臂(19q)(3/11;27%)上发现了缺失,但程度远低于成人OGs中观察到的情况。6例年龄较大患者的肿瘤在1p和/或19q上也有多体性。虽然大多数年龄较大的儿童存活,但有4例复发。奇怪的是,2例患有AOGs的年龄较大儿童在1p和19q上既有缺失又有多体性,但对治疗反应不佳,在一年内死亡。我们得出结论,与成人OGs相比,儿童OGs中1p或19q的改变很少见,在生命的第一个十年出现的OGs中几乎不存在。因此,与成人相比,大多数儿童OGs的发病机制可能涉及不同的遗传途径。显然需要对更大系列进行基因组筛查,以描绘这些罕见儿童肿瘤的独特分子特征。