Ino Y, Betensky R A, Zlatescu M C, Sasaki H, Macdonald D R, Stemmer-Rachamimov A O, Ramsay D A, Cairncross J G, Louis D N
Molecular Neuro-Oncology Laboratory, Department of Pathology and Neurosurgical Service, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Clin Cancer Res. 2001 Apr;7(4):839-45.
In a prior study of anaplastic oligodendrogliomas treated with chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome 1p correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic management was not uniform, loss of 1p did not identify all chemosensitive tumors, nor did all patients whose tumors harbor a 1p loss have long survival.
To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic oligodendrogliomas, we studied a larger, more homogeneous group of 50 patients with histologically defined anaplastic oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy.
We demonstrate that these tumors can be divided genetically into four therapeutically and prognostically relevant subgroups. Patients whose tumors have combined but isolated losses of 1p and 19q have marked and durable responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome 1p alterations also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking 1p loss can also be divided into two subgroups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsive, aggressive tumors that are clinically and genotypically similar to glioblastomas.
These data raise the possibility, for the first time, that therapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic oligodendroglioma.
在先前一项针对间变性少突胶质细胞瘤在诊断时或放疗后复发时接受化疗的研究中，1号染色体短臂（1p）等位基因缺失与更好的化疗反应及总生存期相关。然而，在这组治疗管理并不统一的患者中，1p缺失并不能识别所有对化疗敏感的肿瘤，且并非所有肿瘤存在1p缺失的患者都能长期生存。
为了阐明间变性少突胶质细胞瘤患者诊断时分子遗传学检测的临床相关性，我们研究了一组更大、更具同质性的50例患者，这些患者组织学确诊为间变性少突胶质细胞瘤，以化疗方案作为主要初始治疗。
我们证明这些肿瘤在基因上可分为四个与治疗和预后相关的亚组。肿瘤同时但孤立地存在1p和19号染色体长臂（19q）缺失的患者，无论是否接受术后放疗，对化疗均有显著且持久的反应，并伴有较长生存期。其他存在1号染色体短臂改变的肿瘤对化疗也有反应，但反应持续时间较短，患者生存期也较短。缺乏1p缺失的肿瘤也可分为两个亚组：那些存在TP53突变的肿瘤，可能对化疗也有反应，但复发很快；那些没有TP53突变的肿瘤，对化疗反应不佳，是侵袭性肿瘤，在临床和基因类型上与胶质母细胞瘤相似。
这些数据首次提出了一种可能性，即诊断时的治疗决策可能针对间变性少突胶质细胞瘤的特定基因亚型进行定制。
