CDKN2A point mutations D153spl(c.457G>T) and IVS2+1G>T result in aberrant splice products affecting both p16INK4a and p14ARF
CDKN2A point mutations D153spl(c.457G>T) and IVS2+1G>T result in aberrant splice products affecting both p16INK4a and p14ARF
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CDKN2A 点突变 D153spl(c.457G>T) 和 IVS2 1G>T 导致异常剪接产物影响 p16INK4a 和 p14ARF
DOI：
10.1038/sj.onc.1206564
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发表时间：
2003
期刊：
影响因子：
8
通讯作者：
J. Struewing
中科院分区：
文献类型：
--
作者：
J. Rutter;A. Goldstein;Michael R Dávila;M. Tucker;J. Struewing
编码蛋白质p16 INK 4a和p14 ARF的CDKN 2A基因位于染色体9 p21上。该位点的生殖系突变增加了皮肤恶性黑色素瘤（CMM）的易感性。一般来说，错义和无义突变是导致p16 INK 4a和可能的p14 ARF蛋白功能缺陷的主要原因，占遗传性CMM病例的约20%。我们报告了一个黑色素瘤先证者CDKN 2A-p16 INK 4a基因外显子2最后一个核苷酸的G>T颠换突变，影响了153位天冬氨酸残基。如果剪接不受影响，这种突变将把Asp变成Tyr。然而，RT-PCR分析显示，我们称之为D153 spl（c.457G>T）的突变和先前描述的下一个核苷酸IVS 2 +1G>T的突变导致影响p16 INK 4a和p14 ARF的相同的异常剪接。两种正常转录物中的每一种的两种主要交替剪接产物包括外显子2中的74 bp缺失，揭示了隐蔽剪接位点，以及外显子2的完全跳跃。p16 INK 4a和p14 ARF的双重失活可能是这些家族中CMM的原因之一。
The CDKN2A gene, which encodes the proteins p16INK4a and p14ARF, is located on chromosome 9p21. Germline mutations at this locus increase susceptibility to cutaneous malignant melanoma (CMM). In general, missense and nonsense mutations are primarily responsible for defective p16INK4a and possibly p14ARF protein function and account for ∼20% of inherited CMM cases. We report a G>T transversion mutation in the last nucleotide of exon 2, affecting the aspartic acid residue at position 153 of CDKN2A-p16INK4a in a proband with melanoma. If splicing were unaffected, this mutation would change Asp to Tyr. RT–PCR analysis, however, revealed that this mutation, which we have termed D153spl(c.457G>T), and a previously described mutation at the next nucleotide, IVS2+1G>T, result in identical aberrant splicing affecting both p16INK4a and p14ARF. The two main alternate splice products for each of the two normal transcripts includes a 74 bp deletion in exon 2, revealing a cryptic splice site, and the complete skipping of exon 2. The dual inactivation of p16INK4a and p14ARF may contribute to the CMM in these families.
影响因子：
56.9
作者：
KAMB, A;GRUIS, NA;SKOLNICK, MH
通讯作者：
SKOLNICK, MH