Evolution of germline TP53 variant classification in children with cancer.
Evolution of germline TP53 variant classification in children with cancer.
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DOI：
10.1016/j.cancergen.2022.02.011
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发表时间：
2022-06
期刊：
影响因子：
1.9
通讯作者：
Plon, S. E.
中科院分区：
文献类型：
--
作者：
Tallis, E.;Scollon, S.;Ritter, D. I.;Plon, S. E.
由TP 53中的生殖系致病性变体引起的Li-Fraumeni综合征导致对多种癌症的易感性。鉴于LFS患者的癌症监测改善了生存率，不确定意义的变异（VUS）和变异随时间的重新分类引起了管理问题。我们描述的经验TP 53变异重新分类在儿科癌症中心。方法：我们回顾了德克萨斯州儿童癌症遗传学诊所756例患者的医疗记录（2010-2019）。我们注意到TP 53的初始分类和任何重新分类。然后，我们根据ClinGen TP 53变体管理专家小组的建议，使用来自ClinVar、医学文献和IARC数据库的数据对TP 53变体进行分类。结果：在234例TP 53检测患者中，27例（11.5%）报告包含致病/可能致病（P/LP）变异，7（3%）包含VUS。截至2022年1月，ClinVar中6种独特VUS中的4种和16种独特P/LP变体中的2种改变了解读。ClinVar中这4个VUS的重新解释与初始报告时的临床决策相匹配。应用TP 53 VCEP规范，将3例VUS分类为P/LP/良性，1例致病性变异分类为可能良性。结论：有计划地回顾变异显著性是必要的，特别是对于LFS可能性高的患者。
Li-Fraumeni syndrome, caused by germline pathogenic variants in TP53, results in susceptibility to multiple cancers. Variants of uncertain significance (VUS) and reclassification of variants over time pose management concerns given improved survival with cancer surveillance for LFS patients. We describe the experience of TP53 variant reclassification at a pediatric cancer center. Methods: We reviewed medical records (2010–2019) of 756 patients seen in Texas Children’s Cancer Genetics Clinic. We noted initial TP53 classification and any reclassifications. We then classified TP53 variants following ClinGen TP53 variant curation expert panel recommendations using data from ClinVar, medical literature and IARC database. Results: Of 234 patients tested for TP53, 27 (11.5%) reports contained pathogenic/likely pathogenic (P/LP) variants and 7 (3)% contained VUS. By January 2022, 4 of 6 unique VUS and 2 of 16 unique P/LP variants changed interpretations in ClinVar. Reinterpretation of these 4 VUS in ClinVar matched clinical decision at the time of initial report. Applying TP53 VCEP specifications classified 3 VUS to P/LP/benign, and one pathogenic variant to likely benign. Conclusions: Planned review of variant significance is essential, especially for patients with high probability of LFS.
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影响因子：
3.9
作者：
Rivera-Muñoz EA;Milko LV;Harrison SM;Azzariti DR;Kurtz CL;Lee K;Mester JL;Weaver MA;Currey E;Craigen W;Eng C;Funke B;Hegde M;Hershberger RE;Mao R;Steiner RD;Vincent LM;Martin CL;Plon SE;Ramos E;Rehm HL;Watson M;Berg JS
通讯作者：
Berg JS
影响因子：
30.8
作者：
Holmfeldt, Linda;Wei, Lei;Diaz-Flores, Ernesto;Walsh, Michael;Zhang, Jinghui;Ding, Li;Payne-Turner, Debbie;Churchman, Michelle;Andersson, Anna;Chen, Shann-Ching;McCastlain, Kelly;Becksfort, Jared;Ma, Jing;Wu, Gang;Patel, Samir N.;Heatley, Susan L.;Phillips, Letha A.;Song, Guangchun;Easton, John;Parker, Matthew;Chen, Xiang;Rusch, Michael;Boggs, Kristy;Vadodaria, Bhavin;Hedlund, Erin;Drenberg, Christina;Baker, Sharyn;Pei, Deqing;Cheng, Cheng;Huether, Robert;Lu, Charles;Fulton, Robert S.;Fulton, Lucinda L.;Tabib, Yashodhan;Dooling, David J.;Ochoa, Kerri;Minden, Mark;Lewis, Ian D.;To, L. Bik;Marlton, Paula;Roberts, Andrew W.;Raca, Gordana;Stock, Wendy;Neale, Geoffrey;Drexler, Hans G.;Dickins, Ross A.;Ellison, David W.;Shurtleff, Sheila A.;Pui, Ching-Hon;Ribeiro, Raul C.;Devidas, Meenakshi;Carroll, Andrew J.;Heerema, Nyla A.;Wood, Brent;Borowitz, Michael J.;Gastier-Foster, Julie M.;Raimondi, Susana C.;Mardis, Elaine R.;Wilson, Richard K.;Downing, James R.;Hunger, Stephen P.;Loh, Mignon L.;Mullighan, Charles G.
通讯作者：
Mullighan, Charles G.
影响因子：
3.9
作者：
Olivier, M;Eeles, R;Hainaut, P
通讯作者：
Hainaut, P
影响因子：
51.1
作者：
Villani, Anita;Tabori, Uri;Malkin, David
通讯作者：
Malkin, David
影响因子：
4.6
作者：
Idos, Gregory E.;Kurian, Allison W.;Gruber, Stephen B.
通讯作者：
Gruber, Stephen B.