Early recurrence in standard-risk medulloblastoma patients with the common idic(17)(p11.2) rearrangement
Early recurrence in standard-risk medulloblastoma patients with the common idic(17)(p11.2) rearrangement
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DOI：
10.1093/neuonc/nos086
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发表时间：
2012-07-01
期刊：
影响因子：
15.9
通讯作者：
Perry, Arie
中科院分区：
文献类型：
--
作者：
Bien-Willner, Gabriel A.;Lopez-Terrada, Dolores;Perry, Arie
髓母细胞瘤的诊断是组织学;治疗取决于分期和发病年龄。尽管临床因素可以识别标准和高风险人群，但这些发现无法区分哪些标准风险患者会复发和死亡。结果被认为受肿瘤亚型和分子改变的影响。在一些但不是所有的研究中，预后不良与等染色体（i）17 q相关。在大多数情况下，分子研究证明i17 q不是真正的等臂染色体，而是等双着丝粒染色体，17（17）（p11.2），重排断点位于17 p11.2的REPA/REPB区域内。本研究探讨了使用基于荧光原位杂交（FISH）的检测法检测p11.2重排的临床实用性。该试验应用于58例连续的标准和高危髓母细胞瘤，并进行了至少5年的临床随访。i17 q（即，包括不涉及共同断点的病例）、p11.2和组织学亚型的存在与临床结局相关。总生存期（OS）和无病生存期（DFS）与文献报道一致。14例患者（25例）有i17 q，其中10例（18例）涉及常见的等双着丝粒重排。i17 q的存在与预后不良相关。所有间变性（4例）、不可切除疾病（7例）和出现转移（10例）的病例的OS和DFS均较差;然而，标准风险肿瘤患者的表现更好。在这44例病例中，肿瘤的预后显著较差（17）（p11.2），平均DFS较短。FISH检测到的p11.2可能有助于标准风险患者的风险分层。这种异常染色体的存在与髓母细胞瘤的早期复发有关。
Medulloblastoma is diagnosed histologically; treatment depends on staging and age of onset. Whereas clinical factors identify a standard- and a high-risk population, these findings cannot differentiate which standard-risk patients will relapse and die. Outcome is thought to be influenced by tumor subtype and molecular alterations. Poor prognosis has been associated with isochromosome (i)17q in some but not all studies. In most instances, molecular investigations document that i17q is not a true isochromosome but rather an isodicentric chromosome, idic(17)(p11.2), with rearrangement breakpoints mapping within the REPA/REPB region on 17p11.2. This study explores the clinical utility of testing for idic(17)(p11.2) rearrangements using an assay based on fluorescent in situ hybridization (FISH). This test was applied to 58 consecutive standard- and high-risk medulloblastomas with a 5-year minimum of clinical follow-up. The presence of i17q (ie, including cases not involving the common breakpoint), idic(17)(p11.2), and histologic subtype was correlated with clinical outcome. Overall survival (OS) and disease-free survival (DFS) were consistent with literature reports. Fourteen patients (25) had i17q, with 10 (18) involving the common isodicentric rearrangement. The presence of i17q was associated with a poor prognosis. OS and DFS were poor in all cases with anaplasia (4), unresectable disease (7), and metastases at presentation (10); however, patients with standard-risk tumors fared better. Of these 44 cases, tumors with idic(17)(p11.2) were associated with significantly worse patient outcomes and shorter mean DFS. FISH detection of idic(17)(p11.2) may be useful for risk stratification in standard-risk patients. The presence of this abnormal chromosome is associated with early recurrence of medulloblastoma.