Increased Incidence of Choroid Plexus Carcinoma Due to the Germline TP53 R337H Mutation in Southern Brazil
Increased Incidence of Choroid Plexus Carcinoma Due to the Germline TP53 R337H Mutation in Southern Brazil
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DOI：
10.1371/journal.pone.0018015
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发表时间：
2011-03-22
期刊：
影响因子：
3.7
通讯作者：
Bleggi Torres, Luiz Fernando
中科院分区：
文献类型：
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作者：
Custodio, Gislaine;Taques, Guilherme R.;Bleggi Torres, Luiz Fernando
背景：脉络丛癌（CPC）是一种罕见的肿瘤，主要见于儿童。鉴于巴西南部TP53基因种系R337H突变的高频率，我们评估了儿童CPC家庭中R337H突变的频率。方法/主要发现：本系列纳入了1992年至2010年同一医院收治的29例患者，包括22例CPC患儿（诊断时年龄为0.08-13.6岁）和7例脉络丛乳头状瘤患儿（Pp; 0.5-9.8岁）。手术切除28例。提取血液和/或肿瘤DNA，使用PCR-RFLP进行分析，并通过测序240 bp的TP53外显子10来证实结果。患者、所有家长和部分亲属提交了血样DNA分析。此外，我们还检查了石蜡包埋肿瘤样本中DNA突变的存在，以评估杂合性的损失。我们发现63.3%（14/22）的CPC患者种系R337H突变阳性；CPC样本要么是杂合的（n = 7），要么只丢失了野生型（n = 4），要么只有R337H拷贝（n = 2）。没有一个CPC样品。所有Pp病例（7/7,100%）R337H阴性。治愈(。在携带R337H突变的CPC病例中，18.1%（2/11）、71.4%（5/7）和25%（2/8）未携带R337H突变的CPC病例中，5年无疾病生存（无疾病生存）。有2例或2例以上癌症家族史的亲本侧分离R337H突变，其中50%（7/14）与li - fraumeni样综合征相容。意义：我们的研究结果首次表明，R337H TP53突变导致63%的儿童CPC病例，表明巴西南部CPC发病率较高。
Background: Choroid plexus carcinomas (CPC) are rare tumors predominantly found in children. Given the high frequency of the germline R337H mutation in the TP53 gene in southern Brazil, we have evaluated the frequency of the R337H mutation in families with CPC in children.Methodology/Principal Findings: The present series included 29 patients that were admitted to the same institution from 1992 to 2010, including 22 children with CPC (0.08-13.6 years of age at diagnosis) and 7 children with papilloma of the choroid plexus (Pp; 0.5-9.8 years of age). Surgical resection was possible in 28 children. Blood and/or tumor DNA was extracted and analyzed using PCR-RFLP and results were confirmed by sequencing 240 bp of the TP53 exon 10. The patients, all parents, and some relatives submitted samples for blood DNA analysis. In addition, we have also examined the presence of the mutation in DNA from paraffin-embedded tumor samples to evaluate loss of heterozygosity. We found 63.3% (14/22) of the CPC patients positive for the germline R337H mutation; CPC samples were either heterozygous (n = 7), lost only the wild-type (n = 4), or only the R337H copy (n = 2). One CPC sample was not available. All Pp cases (7/7, 100%) were negative for R337H. Cure (. 5 years survival free of disease) was observed in 18.1% of the CPC cases with the R337H mutation (2/11), 71.4% of the Pp (5/7), and 25% of CPC cases negative for the R337H mutation (2/8). Family history of cancer (with 2 or more cancer cases) was exclusively identified on the parental side segregating the R337H mutation, and 50% (7/14) of them were compatible with Li-Fraumeni-like syndrome.Significance: Our results show for the first time that the R337H TP53 mutation is responsible for 63% of the CPC cases in children, suggesting a higher incidence of CPC in southern Brazil.