神经母细胞瘤中1p36常见缺失区域内CAMTA1和FLJ10737的等位基因变体。

Allelic variants of CAMTA1 and FLJ10737 within a commonly deleted region at 1p36 in neuroblastoma.

作者信息

Henrich Kai-Oliver, Claas Andreas, Praml Christian, Benner Axel, Mollenhauer Jan, Poustka Annemarie, Schwab Manfred, Westermann Frank

机构信息

Division of Tumour Genetics B030, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

出版信息

Eur J Cancer. 2007 Feb;43(3):607-16. doi: 10.1016/j.ejca.2006.09.023. Epub 2007 Jan 11.

DOI:10.1016/j.ejca.2006.09.023

PMID:17222547

Abstract

Deletion of a distal portion of 1p is seen in a wide range of human malignancies, including neuroblastoma. Here, a 1p36.3 commonly deleted region of 216 kb has been defined encompassing two genes, CAMTA1 and FLJ10737. Low expression of CAMTA1 has been recently shown to be an independent predictor of poor outcome in neuroblastoma patients. The present study surveys CAMTA1 and FLJ10737 for genetic alterations by fluorescence-based single strand conformation polymorphism (SSCP) using a panel of DNAs from 88 neuroblastomas, their matching blood samples and 97 unaffected individuals. Nucleotide variants encoding amino acid substitutions were found in both genes. One CAMTA1 variant (T1336I) was not detected in 97 unaffected individuals, another (N1177K) resides in a conserved domain of the CAMTA1 protein and was found hemizygous in six neuroblastomas. We found no evidence for somatic mutations in FLJ10737 or CAMTA1. Further investigations are needed to address the functional impact of the identified variants and their possible significance for neuroblastoma.

摘要

1p远端部分的缺失在包括神经母细胞瘤在内的多种人类恶性肿瘤中都有发现。在此，已确定一个216 kb的1p36.3常见缺失区域，该区域包含两个基因，即CAMTA1和FLJ10737。最近研究表明，CAMTA1低表达是神经母细胞瘤患者预后不良的独立预测指标。本研究使用来自88例神经母细胞瘤及其匹配血样以及97例未受影响个体的DNA样本，通过基于荧光的单链构象多态性（SSCP）技术，对CAMTA1和FLJ10737的基因改变进行了检测。在这两个基因中均发现了编码氨基酸替换的核苷酸变异。一种CAMTA1变异（T1336I）在97例未受影响个体中未被检测到，另一种变异（N1177K）位于CAMTA1蛋白的一个保守结构域中，在6例神经母细胞瘤中发现为半合子状态。我们未发现FLJ10737或CAMTA1存在体细胞突变的证据。需要进一步研究以确定所识别变异的功能影响及其对神经母细胞瘤的潜在意义。