Microsatellite alterations and TP53 mutations in plasma DNA of small-cell lung cancer patients:: Follow-up study and prognostic significance
Microsatellite alterations and TP53 mutations in plasma DNA of small-cell lung cancer patients:: Follow-up study and prognostic significance
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DOI：
10.1023/a:1008305412635
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发表时间：
2000-09-01
影响因子：
50.5
通讯作者：
Bonilla, F
中科院分区：
文献类型：
--
作者：
Gonzalez, R;Silva, JM;Bonilla, F
背景：小细胞肺癌（Small-cell lung cancer， SCLC）是肺癌的主要类型之一，与许多不同的体细胞分子遗传变化有关。在肿瘤DNA中观察到的这些改变，也在患者的血浆DNA中被发现。我们进行本研究是为了对血浆DNA异常与患者生存之间的关系进行前瞻性研究。患者和方法：经组织学诊断的SCLC患者35例。选择多态性标记（ACTBP2， UT762和AR），因为它们在SCLC中报道的高变化率，并在肿瘤组织，正常血细胞和血浆DNA中进行分析。此外，我们在肿瘤和血浆DNA中寻找TP53基因的突变。结果：在25例（71%）患者的血浆DNA中检测到至少一个与原发肿瘤精确匹配的分子变化。血浆DNA异常患者和血浆DNA无改变患者的生存期无差异。然而，伴随微卫星修饰和TP53突变的患者与仅携带其中一种分子变化的患者相比，生存率有显著差异（P = 0.02）。在15例病例中，可能发现肿瘤反应与异常血浆DNA的消失或肿瘤进展与血浆DNA改变的持续存在之间的相关性。结论：游离血浆DNA分子改变在SCLC患者血浆DNA中存在程度很高，可能是一个预后因素。
Background: Small-cell lung cancer (SCLC), one of the major types of lung cancer, is associated with many different somatic molecular genetic changes. These alterations, observed in tumor DNA, have also been identified in the plasma DNA of patients. We undertook the present study to make a prospective investigation into the correlation between abnormal plasma DNA and patient survival.Patients and methods: Thirty-five patients with SCLC were selected after histological diagnosis. Polymorphic markers (ACTBP2, UT762 and AR) were chosen for their reported high rate of alterations in SCLC and analyzed in tumor tissue, normal blood cells and plasma DNA. Furthermore, we looked for mutations of the TP53 gene in tumor and plasma DNA.Results: In 25 patients (71%) at least one molecular change precisely matching that of the primary tumor was detected in the plasma DNA. No difference in survival was observed between patients with aberrant plasma DNA and patients without plasma DNA alterations. However, patients with microsatellite modifications and TP53 mutations concomitantly, showed a significant difference (P = 0.02) in survival compared with patients bearing only one of these molecular changes. In 15 cases it was possible to find a correlation either between tumor response and disappearance of abnormal plasma DNA, or tumor progression and persistence of plasma DNA alterations.Conclusions: Free plasma DNA with molecular alterations is present to a high degree in plasma DNA of SCLC patients and may have a role as a prognostic factor.