Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei: a comprehensive genetic profiling and survival analysis
Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei: a comprehensive genetic profiling and survival analysis
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DOI：
10.1038/jhg.2013.132
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发表时间：
2014-03-01
影响因子：
3.5
通讯作者：
Miller, Robert C.
中科院分区：
文献类型：
--
作者：
Sio, Terence T.;Mansfield, Aaron S.;Miller, Robert C.
腹膜假粘液瘤（PMP）是一种罕见的腹部恶性肿瘤。我们假设下一代外显子测序将识别可能具有预后或治疗意义的复发突变。根据组织的可用性和充分的随访选择了十名患者。他们于 2002 年 9 月至 2004 年 8 月期间在我们机构接受治疗。使用新一代外显子测序，我们在福尔马林固定石蜡包埋的载玻片中测试了 236 个癌症相关基因的突变。另外还通过免疫组织化学染色测试了 MCL1 扩增。在 8 名患者 (80%) 中发现了可检测的突变。 7 名患者携带 KRAS 突变，最常见的是密码子 12。还检测到了 4 种 GNAS 突变（R201H/R201C 替换）。 MCL1 和 JUN 在三名患者中同时扩增。一名 MCL1 和 JUN 扩增的患者同时出现 MYC 和 NFKBIA 扩增。 ZNF703 在一名患者体内得到扩增。免疫组化也发现MCL1扩增的患者表达MCL1，但在一些不扩增的患者中也检测到MCL1表达。据我们所知，我们是第一个在 PMP 中报告 MCL1 和 JUN 共扩增的人。 MCL1 的表达可能不完全依赖于扩增。这些反复发生的突变事件的预后和治疗意义是正在进行的研究的主题。
Pseudomyxoma peritonei (PMP) is a rare abdominal malignancy. We hypothesized that next-generation exomic sequencing would identify recurrent mutations that may have prognostic or therapeutic implications. Ten patients were selected on the basis of availability of tissue and adequate follow-up. They were treated at our institution between September 2002 and August 2004. Using next-generation exomic sequencing, we tested for mutations in 236 cancer-related genes in formalin-fixed paraffin-embedded slides. MCL1 amplification was additionally tested with immunohistochemical staining. Detectable mutations were found in 8 patients (80%). Seven patients harbored a KRAS mutation, most commonly involving codon 12. Four GNAS mutations (R201H/R201C substitutions) were also detected. MCL1 and JUN were concurrently amplified in three patients. One patient with MCL1 and JUN amplification had concurrent amplification of MYC and NFKBIA. ZNF703 was amplified in one patient. Patients with MCL1 amplification were also found to express MCL1 with immunohistochemistry, but MCL1 expression was also detected in some patients without amplification. To our knowledge, we are the first to report MCL1 and JUN coamplification in PMP. Expression of MCL1 may not be completely dependent on amplification. The prognostic and therapeutic implications of these recurrent mutational events are the subject of ongoing investigation.