AbstractA germline alteration in the PTEN gene causes a spectrum of disorders conceptualized as PTEN hamartoma tumor syndrome (PHTS), which show high risk of tumor development and a highly variable and complex phenotype. The diagnosis of PHTS is established in a proband by identification of a heterozygous germline PTEN pathogenic variant on molecular genetic testing.

摘要PTEN基因的种系改变会导致一系列概念为PTEN错构瘤肿瘤综合征（PHTS）的疾病，这些疾病显示出肿瘤发展的高风险以及高度可变和复杂的表型。通过在分子遗传学测试中鉴定杂合种系PTEN致病变体，在先证者中建立了PHTS的诊断。

In this study, to understand more PTEN-associated clinical phenotype and PHTS in a Japanese population, we extracted 128 germline PTEN rare variants from 113,535 adult Japanese registered in Biobank Japan (BBJ), and categorized 29 pathogenic/likely pathogenic variants in 30 individuals (0.0264%) with ClinVar classifications and ACMG/AMP guideline for PTEN.

在这项研究中，为了了解日本人群中更多与PTEN相关的临床表型和PHTS，我们从日本生物银行（BBJ）注册的113535名成年日本人中提取了128个种系PTEN罕见变体，并根据ClinVar分类和ACMG/AMP PTEN指南对30名个体（0.0264%）中的29种致病/可能致病变体进行了分类。

We examined case-control association in 75,238 patients with various types of cancer and 38,297 non-cancer controls, and identified that PTEN pathogenic variants (PVs) were significantly associated with endometrial cancer (OR = 35.7, P = 9.73E-04) and marginally associated with female breast cancer (OR = 19.5, P = 3.92E-03), especially at young onset and with multiple cancers.

我们检查了75238例不同类型癌症患者和38297例非癌症对照的病例对照关联，发现PTEN致病变异（PVs）与子宫内膜癌（OR）显着相关 = 35.7, P=9.73E-04），与女性乳腺癌略有相关（OR=19.5，P=3.92E-03），尤其是在年轻发病和多种癌症时。

We observed that among the 127 disease phenotypes the PTEN PV carriers had uterine fibroid, goiter, ovarian cyst, and epilepsy, which is consistent with PTEN-related phenotypes. We also found that weight/height were significantly higher in adult female carriers with PTEN PV (P = 3.1E-04 and P = 0.0014, respectively), which is consistent with overgrowth syndrome of PHTS.

我们观察到，在127种疾病表型中，PTEN PV携带者患有子宫肌瘤，甲状腺肿，卵巢囊肿和癫痫病，这与PTEN相关表型一致。我们还发现PTEN PV成年女性携带者的体重/身高显着更高（P=3.1E-04和P = 0.0014, 分别），这与PHTS的过度生长综合征一致。

Our results indicate the phenotypical features associated with PTEN PVs in a Japanese population, especially female, and can contribute to the screening for PTEN variants and its associated several phenotypes..

我们的结果表明，日本人群（尤其是女性）中与PTEN PVs相关的表型特征，可以有助于筛选PTEN变体及其相关的几种表型。。

Access through your institution

通过您的机构访问

Buy or subscribe

购买或订阅

This is a preview of subscription content, access via your institution

这是订阅内容的预览，可通过您的机构访问

Access options

访问选项

Access through your institution

通过您的机构访问

Access through your institution

通过您的机构访问

Change institution

变革机构

Buy or subscribe

购买或订阅

Subscribe to this journal

订阅此日记

Receive 12 print issues and online access

接收12个打印问题和在线访问

251,40 € per year

每年251,40欧元

only 20,95 € per issue

每期仅20,95欧元

Learn more

了解更多信息

Buy this article

购买这篇文章

Purchase on SpringerLink

在SpringerLink上购买

Instant access to full article PDF

即时访问全文PDF

Buy now

立即购买

Prices may be subject to local taxes which are calculated during checkout

价格可能需要缴纳结帐时计算的地方税

Additional access options:

其他访问选项：

Log in

登录

Learn about institutional subscriptions

了解机构订阅

Read our FAQs

阅读我们的常见问题

Contact customer support

Fig. 1Fig. 2Fig. 3

图1图。图2。3

ReferencesPezzolesi MG, Zbuk KM, Waite KA, Eng C. Comparative genomic and functional analyses reveal a novel cis-acting PTEN regulatory element as a highly conserved functional E-box motif deleted in Cowden syndrome. Hum Mol Genet. 2007;16:1058–71.Article

参考文献Pezzolesi MG，Zbuk KM，Waite KA，Eng C。比较基因组和功能分析揭示了一种新型顺式作用PTEN调控元件，它是Cowden综合征中缺失的高度保守的功能性E-box基序。哼，摩尔基因。；16： 1058-71.条

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 2009;4:127–50.Article

Chalhoub N，Baker SJ。PTEN和癌症中的PI3激酶途径。Annu Rev Pathol公司。2009年；4： 127-50.文章

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Waite KA, Eng C. Protean PTEN: form and function. Am J Hum Genet. 2002;70:829–44.Article

Waite KA，Eng C.Protean PTEN：形式和功能。我是J Hum Genet。2002年；70:829–44.文章

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Yehia L, Keel E, Eng C. The clinical spectrum of PTEN mutations. Annu Rev Med. 2020;71:103–16.Article

Yehia L，Keel E，Eng C.PTEN突变的临床谱。Annu Rev Med。2020；

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yehia L, Eng C. 65 years of the double helix: one gene, many endocrine and metabolic syndromes: PTEN-opathies and precision medicine. Endocr Relat Cancer. 2018;25:T121–40.Article

Yehia L，Eng C。65年的双螺旋：一个基因，许多内分泌和代谢综合征：PTEN病和精准医学。内分泌相关癌症。2018年；25:T121-40.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, et al. A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. Am J Hum Genet. 2011;88:42–56.Article

Tan MH，Mester J，Peterson C，Yang Y，Chen JL，Rybicki LA等。基于对3042名先证者的前瞻性研究，提出了一种用于选择PTEN突变检测患者的临床评分系统。我是J Hum Genet。2011年；88:42–56.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cummings S, Alfonso A, Hughes E, Kucera M, Mabey B, Singh N, et al. Cancer risk associated with PTEN pathogenic variants identified using multigene hereditary cancer panel testing. JCO Precis Oncol. 2023;7:e2200415.Hendricks LAJ, Hoogerbrugge N, Venselaar H, Aretz S, Spier I, Legius E, et al.

Cummings，Alfonso A，Hughes E，Kucera M，Mabey B，Singh N等人。使用多基因遗传性癌症专家组测试鉴定与PTEN致病变异相关的癌症风险。JCO Precis Oncol。2023年；7： e2200415。Hendricks LAJ，Hoogerbrugge N，Venselaar H，Aretz S，Spier I，Legius E等。

Genotype-phenotype associations in a large PTEN Hamartoma Tumor Syndrome (PHTS) patient cohort. Eur J Med Genet. 2022;65:104632.Article .

大型PTEN错构瘤肿瘤综合征（PHTS）患者队列中的基因型与表型关联。Eur J Med Genet。2022年；65:104632。第条。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Trost B, Thiruvahindrapuram B, Chan AJS, Engchuan W, Higginbotham EJ, Howe JL, et al. Genomic architecture of autism from comprehensive whole-genome sequence annotation. Cell. 2022;185:4409–27.e18.Article

Trost B，Thiruvahindrapuram B，Chan AJS，Engchuan W，Higginbotham EJ，Howe JL等。来自全面全基因组序列注释的自闭症基因组结构。细胞。2022年；

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, et al. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014;42:D980–5.Article

Landrum MJ，Lee JM，Riley GR，Jang W，Rubinstein WS，Church DM等。ClinVar：序列变异与人类表型之间关系的公共档案。核酸Res.2014；42:D980–5.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Mester JL, Ghosh R, Pesaran T, Huether R, Karam R, Hruska KS, et al. Gene-specific criteria for PTEN variant curation: recommendations from the ClinGen PTEN Expert Panel. Hum Mutat. 2018;39:1581–92.Article

Mester JL，Ghosh R，Pesaran T，Huether R，Karam R，Hruska KS等。PTEN变异管理的基因特异性标准：ClinGen PTEN专家组的建议。嗡嗡声突变。2018年；39:1581–92.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Okawa Y, Iwasaki Y, Johnson TA, Ebata N, Inai C, Endo M, et al. Hereditary cancer variants and homologous recombination deficiency in biliary tract cancer. J Hepatol. 2023;78:333–42.Article

Okawa Y，Iwasaki Y，Johnson TA，Ebata N，Inai C，Endo M等。胆道癌的遗传性癌症变异和同源重组缺陷。J Hepatol。2023年；78:333–42.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, et al. Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nat Commun. 2018;9:4083.Article

Momozawa Y，Iwasaki Y，Parsons MT，Kamatani Y，Takahashi A，Tamura C等。7051名日本患者和11241名对照中11种乳腺癌基因的种系致病变异。纳特公社。2018年；9： 第4083条

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fujita M, Liu X, Iwasaki Y, Terao C, Mizukami K, Kawakami E, et al. Population-based screening for hereditary colorectal cancer variants in Japan. Clin Gastroenterol Hepatol. 2022;20:2132–41.e9.Article

Fujita M，Liu X，Iwasaki Y，Terao C，Mizukami K，Kawakami E等。日本基于人群的遗传性结直肠癌变异筛查。临床胃肠肝病。2022年；20：

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Usui Y, Taniyama Y, Endo M, Koyanagi YN, Kasugai Y, Oze I, et al. Helicobacter pylori, homologous-recombination genes, and gastric cancer. N. Engl J Med. 2023;388:1181–90.Article

Usui Y，Taniyama Y，Endo M，Koyanagi YN，Kasugai Y，Oze I等。幽门螺杆菌，同源重组基因和胃癌。N、 英国医学杂志2023；388:1181–90.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hirata M, Kamatani Y, Nagai A, Kiyohara Y, Ninomiya T, Tamakoshi A, et al. Cross-sectional analysis of BioBank Japan clinical data: a large cohort of 200,000 patients with 47 common diseases. J Epidemiol. 2017;27:S9–s21.Article

。J流行病学。2017年；27:S9–s21.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Nagai A, Hirata M, Kamatani Y, Muto K, Matsuda K, Kiyohara Y, et al. Overview of the BioBank Japan project: study design and profile. J Epidemiol. 2017;27:S2–8.Article

Nagai A，Hirata M，Kamatani Y，Muto K，Matsuda K，Kiyohara Y等。日本生物银行项目概述：研究设计和概况。J流行病学。2017年；27:S2-8.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Buys SS, Sandbach JF, Gammon A, Patel G, Kidd J, Brown KL, et al. A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer. 2017;123:1721–30.Article

。癌症。2017年；123:1721–30.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chen S, Francioli LC, Goodrich JK, Collins RL, Kanai M, Wang Q, et al. A genomic mutational constraint map using variation in 76,156 human genomes. Nature 2024;625:92–100.Article

Chen S，Francioli LC，Goodrich JK，Collins RL，Kanai M，Wang Q等。使用76156个人类基因组变异的基因组突变约束图。自然2024；625:92–100.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Cingolani P, Platts A, Wang le L, Coon M, Nguyen T, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly. 2012;6:80–92.Article

Cingolani P，Platts A，Wang le L，Coon M，Nguyen T，Wang L等。注释和预测单核苷酸多态性影响的程序，SnpEff：黑腹果蝇w1118株基因组中的SNP；iso-2；iso-3。飞行。2012年；6： 80-92.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jaganathan K, Kyriazopoulou Panagiotopoulou S, McRae JF, Darbandi SF, Knowles D, Li YI, et al. Predicting splicing from primary sequence with deep learning. Cell. 2019;176:535–48.e24.Article

Jaganathan K，Kyriazopoulou Panagiotopoulou S，McRae JF，Darbandi SF，Knowles D，Li YI等。通过深度学习预测一级序列的剪接。细胞。；176:535–48.e24.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Steinhaus R, Proft S, Schuelke M, Cooper DN, Schwarz JM, Seelow D. MutationTaster2021. Nucleic Acids Res. 2021;49:W446–51.Article

Steinhaus R，Proft S，Schuelke M，Cooper DN，Schwarz JM，Seelow D.MutationTaster2021。；49:W446-51.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hess M, Keul F, Goesele M, Hamacher K. Addressing inaccuracies in BLOSUM computation improves homology search performance. BMC Bioinforma. 2016;17:189.Article

Hess M，Keul F，Goesele M，Hamacher K.解决BLOSUM计算中的不准确问题提高了同源搜索性能。BMC生物信息学。2016年；17： 第189条

Google Scholar

谷歌学者

Mighell TL, Evans-Dutson S, O’Roak BJ. A saturation mutagenesis approach to understanding PTEN Lipid phosphatase activity and genotype-phenotype relationships. Am J Hum Genet. 2018;102:943–55.Article

Mighell TL，Evans Dutson S，O'Roak BJ。了解PTEN脂质磷酸酶活性和基因型-表型关系的饱和诱变方法。我是J Hum Genet。2018年；102:943–55.文章

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Matreyek KA, Stephany JJ, Ahler E, Fowler DM. Integrating thousands of PTEN variant activity and abundance measurements reveals variant subgroups and new dominant negatives in cancers. Genome Med. 2021;13:165.Article

Matreyek KA，Stephany JJ，Ahler E，Fowler DM。整合数千个PTEN变异活性和丰度测量结果，揭示了癌症中的变异亚组和新的显性阴性。基因组医学2021；13： 第165条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Matreyek KA, Starita LM, Stephany JJ, Martin B, Chiasson MA, Gray VE, et al. Multiplex assessment of protein variant abundance by massively parallel sequencing. Nat Genet. 2018;50:874–82.Article

Matreyek KA，Starita LM，Stephany JJ，Martin B，Chiasson MA，Gray VE等。通过大规模平行测序对蛋白质变体丰度进行多重评估。纳特·吉内特。2018年；50:874–82.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ou J, Zhu LJ. trackViewer: a Bioconductor package for interactive and integrative visualization of multi-omics data. Nat Methods. 2019;16:453–4.Article

欧J，朱LJ。trackViewer：用于多组学数据交互式和集成可视化的Bioconductor软件包。Nat方法。；16： 453-4.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sato N, Tsunoda H, Nishida M, Morishita Y, Takimoto Y, Kubo T, et al. Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary.

Sato N，Tsunoda H，Nishida M，Morishita Y，Takimoto Y，Kubo T等。卵巢良性子宫内膜囊肿中10q23.3杂合性的丧失和抑癌基因PTEN的突变：从良性子宫内膜囊肿到子宫内膜样癌和卵巢透明细胞癌的可能序列进展。

Cancer Res. 2000;60:7052–6.CAS .

癌症研究2000；60:7052-6。科学院。

PubMed

PubMed

Google Scholar

谷歌学者

Plamper M, Schreiner F, Gohlke B, Kionke J, Korsch E, Kirkpatrick J, et al. Thyroid disease in children and adolescents with PTEN hamartoma tumor syndrome (PHTS). Eur J Pediatr. 2018;177:429–35.Article

Plamper M，Schreiner F，Gohlke B，Kionke J，Korsch E，Kirkpatrick J等。患有PTEN错构瘤肿瘤综合征（PHTS）的儿童和青少年的甲状腺疾病。欧洲儿科杂志。2018年；177:429–35.文章

PubMed

PubMed

Google Scholar

谷歌学者

Keppler-Noreuil KM, Parker VE, Darling TN, Martinez-Agosto JA. Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies. Am J Med Genet C Semin Med Genet. 2016;172:402–21.Article

Keppler Noreuil KM，Parker VE，Darling TN，Martinez Agosto JA。PI3K/AKT/mTOR途径的体细胞过度生长障碍和治疗策略。Am J Med Genet C Semin Med Genet。2016年；172:402–21.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Govatati S, Kodati VL, Deenadayal M, Chakravarty B, Shivaji S, Bhanoori M. Mutations in the PTEN tumor gene and risk of endometriosis: a case-control study. Hum Reprod. 2014;29:324–36.Article

Govatati S，Kodati VL，Deenadayal M，Chakravarty B，Shivaji S，Bhanoori M.PTEN肿瘤基因突变与子宫内膜异位症风险：病例对照研究。嗡嗡声。2014年；29:324–36.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Saskin A, Fulginiti V, Birch AH, Trakadis Y. Prevalence of four Mendelian disorders associated with autism in 2392 affected families. J Hum Genet. 2017;62:657–9.Article

Saskin A，Fulginiti V，Birch AH，Trakadis Y.在2392个受影响家庭中与自闭症相关的四种孟德尔疾病的患病率。J哼哼Genet。2017年；62:657–9.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Serôdio M, Calvão-Pires P, Zhang D, Sá F. Epilepsy in Cowden syndrome: beyond lhermitte-duclos disease. Acta Neurol Belg. 2023;123:2035–7.Article

Serôdio M，Calvão-Pires P，Zhang D，SáF.Cowden综合征的癫痫：超越lhermitte-duclos病。神经学报。2023年；123:2035–7.文章

PubMed

PubMed

Google Scholar

谷歌学者

Plamper M, Gohlke B, Schreiner F, Woelfle J. Phenotype-driven diagnostic of PTEN Hamartoma Tumor Syndrome: macrocephaly, but neither height nor weight development, is the important trait in children. Cancers. 2019;11:975.Article

Plamper M，Gohlke B，Schreiner F，Woelfle J.表型驱动的PTEN错构瘤肿瘤综合征诊断：大头畸形，但身高和体重发育都不是儿童的重要特征。癌症。；11： 第975条

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Woods NT, Baskin R, Golubeva V, Jhuraney A, De-Gregoriis G, Vaclova T, et al. Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. NPJ. Genom Med. 2016;1:16001.CAS

Woods NT，Baskin R，Golubeva V，Jhuraney A，De Gregoriis G，Vaclova T等。功能测定为不确定意义的遗传变异的临床注释提供了强大的工具。NPJ公司。基因组医学2016；1： 16001.CAS

Google Scholar

谷歌学者

Download referencesAcknowledgementsThis work was supported by RIKEN Junior Research Associate Program (Y.K.). We thank the individuals who participated BioBank Japan. We also acknowledge the staff of the Laboratory for Genotyping Development in RIKEN, the RIKEN-IMS genome platform, and the BioBank Japan project.

下载参考文献致谢这项工作得到了RIKEN初级研究助理计划（Y.K.）的支持。我们感谢参加日本生物银行的个人。我们还感谢RIKEN基因分型开发实验室，RIKEN-IMS基因组平台和日本生物银行项目的工作人员。

We are deeply grateful to the late Professor Charis Eng in Cleveland Clinic for her valuable advice on this work and her great contribution to PTEN research. Her memory continues to inspire.FundingThis work was supported by AMED under Grant Numbers JP19kk0305010, JP20ck0106402, JP19cm0106605, and 20ck0106553.Author informationAuthors and AffiliationsLaboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanYuki Kanazashi, Shota Sasagawa, Todd A.

我们非常感谢克利夫兰诊所已故的Charis Eng教授对这项工作的宝贵建议以及她对PTEN研究的巨大贡献。她的记忆继续激励着她。资助这项工作得到了AMED的支持，资助号为JP19kk0305010，JP20ck0106402，JP19cm0106605和20ck0106553。作者信息作者和附属机构癌症基因组学实验室，日本横滨理研综合医学科学中心，日本金泽市，佐川县，托德A。

Johnson, Kazuhiro Maejima & Hidewaki NakagawaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, JapanYuki Kanazashi, Naomichi Matsumoto, Yukihide Momozawa & Hidewaki NakagawaLaboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanYoshiaki Usui, Yusuke Iwasaki, Mikiko Endo, Mitsuyo Yamaguchi & Yukihide MomozawaDivision of Genome Biology, National Cancer Center Research Institute, Tokyo, JapanKouya Shiraishi & Takashi KohnoDepartment of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, JapanTeruhiko Yoshida & Kokichi SuganoDapartment of Genetic Medicine, Kyoundo Hospital, Sasaki Foundation, Tokyo, JapanKokichi SuganoDapartment of Molecular Biology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo, JapanYoshinori MurakamiLaboratory of Complex Trail Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sc.

Johnson，Kazuhiro Maejima&Hidewaki Nakagawa人类遗传学系，横滨市立大学医学研究生院，横滨，日本金崎，松本直美，小泽和中川英武基因分型开发实验室，日本综合医学科学理研中心，横滨，日本小井，岩崎裕介，远藤美子，山口三雄和小泽基因生物学系，日本国立癌症中心研究所，东京医学与服务，日本国立癌症中心医院，东京，日本吉田和高崎杉木遗传医学公寓，京都医院，佐佐木基金会，东京，日本医学院，日本医学院，日本高级医学研究所，分子生物学，分子生物学公寓，日本医学院，东京，JapanYoshinori MurakamiLaboratory of Complex Trail Genomics，Department of Computational Biology and Medical Sciences，Graduate School of Frontier Sc。

PubMed Google ScholarYoshiaki UsuiView author publicationsYou can also search for this author in

PubMed Google ScholarYoshiaki UsuiView作者出版物您也可以在

PubMed Google ScholarYusuke IwasakiView author publicationsYou can also search for this author in

PubMed Google ScholarYusuke IwasakiView作者出版物您也可以在

PubMed Google ScholarShota SasagawaView author publicationsYou can also search for this author in

PubMed Google ScholarShota SasagawaView作者出版物您也可以在

PubMed Google ScholarMikiko EndoView author publicationsYou can also search for this author in

PubMed Google Scholarmakiko EndoView作者出版物您也可以在

PubMed Google ScholarMitsuyo YamaguchiView author publicationsYou can also search for this author in

PubMed Google Scholarmamitsuyo YamaguchiView作者出版物您也可以在

PubMed Google ScholarTodd A. JohnsonView author publicationsYou can also search for this author in

PubMed Google ScholarTodd A.JohnsonView作者出版物您也可以在

PubMed Google ScholarKazuhiro MaejimaView author publicationsYou can also search for this author in

PubMed Google ScholarKazuhiro MaejimaView作者出版物您也可以在

PubMed Google ScholarKouya ShiraishiView author publicationsYou can also search for this author in

PubMed Google ScholarKouya ShiraishiView作者出版物您也可以在

PubMed Google ScholarTakashi KohnoView author publicationsYou can also search for this author in

PubMed Google ScholarTakashi KohnoView作者出版物您也可以在

PubMed Google ScholarTeruhiko YoshidaView author publicationsYou can also search for this author in

PubMed Google ScholarKokichi SuganoView author publicationsYou can also search for this author in

PubMed Google ScholarKokichi SuganoView作者出版物您也可以在

PubMed Google ScholarYoshinori MurakamiView author publicationsYou can also search for this author in

PubMed Google ScholarYoshinori MurakamiView作者出版物您也可以在

PubMed Google ScholarYoichiro KamataniView author publicationsYou can also search for this author in

PubMed Google ScholarYoichiro KamataniView作者出版物您也可以在

PubMed Google ScholarNaomichi MatsumotoView author publicationsYou can also search for this author in

PubMed Google ScholarNaomichi MatsumotoView作者出版物您也可以在

PubMed Google ScholarKoichi MatsudaView author publicationsYou can also search for this author in

PubMed Google ScholarKoichi MatsudaView作者出版物您也可以在

PubMed Google ScholarYukihide MomozawaView author publicationsYou can also search for this author in

PubMed Google ScholarYukihide MomozawaView作者出版物您也可以在

PubMed Google ScholarHidewaki NakagawaView author publicationsYou can also search for this author in

PubMed Google ScholarHidewaki NakagawaView作者出版物您也可以在

PubMed Google ScholarContributionsY.M.O. and H.N. conceived and designed the study. Y.M.O., Y.M.U., Y.K., and K.M. managed the materials in B.B.J., M.E., Y.I., M.Y., and Y.M.O. produced sequence data, and Y.I. and Y.U. performed data curation. Y.K. performed data analysis and statistical tests.

PubMed谷歌学术贡献。M、 O.和H.N.构思并设计了这项研究。Y、 。Y、 K.进行数据分析和统计测试。

S.S., T.J., and Y.I. assisted the variant annotation and case-control analysis. K.S., T.K., T.Y, and K.S. assisted with the data interpretation. K.S., T.K., and Y.Mo. obtained the funding. Y.K. and H.N. wrote the initial draft of the manuscript. N.M., Y.Mo., and H.N. supervised the study. All authors reviewed this manuscript.Corresponding authorsCorrespondence to.

S、 S.，T.J。和Y.I.协助了变体注释和病例对照分析。K、 S.，T.K.，T.Y和K.S.协助数据解释。K、 美国、T.K.和Y.Mo.获得了资金。Y、 K.和H.N.撰写了手稿的初稿。N、 M.，Y.Mo。和H.N.监督了这项研究。所有作者都审阅了这份手稿。通讯作者通讯。

Yukihide Momozawa or Hidewaki Nakagawa.Ethics declarations

Momozawa或Hidewaki Nakagawa。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

。

Ethics approval and consent to participate

道德批准和同意参与

All participants provided written informed consent. The study was approved by the ethical committees of the Institute of Medical Sciences, University of Tokyo, and RIKEN Center for Integrative Medical Sciences.

所有参与者都提供了书面知情同意书。这项研究得到了东京大学医学科学研究所伦理委员会和理研综合医学中心的批准。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplementary Tables S1-9Supplementary Figures S1-6Rights and permissionsSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this articleCite this articleKanazashi, Y., Usui, Y., Iwasaki, Y.

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充表S1-9补充数字S1-6权利和许可Pringer Nature或其许可人（例如协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Kanazashi，Y.，Usui，Y.，Iwasaki，Y。

et al. Cancer and disease profiles for PTEN pathogenic variants in Japanese population..

等人。日本人群中PTEN致病变异的癌症和疾病概况。。

J Hum Genet (2024). https://doi.org/10.1038/s10038-024-01311-zDownload citationReceived: 01 November 2024Revised: 29 November 2024Accepted: 04 December 2024Published: 12 December 2024DOI: https://doi.org/10.1038/s10038-024-01311-zShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

J Hum Genet（2024）。https://doi.org/10.1038/s10038-024-01311-zDownload引文接收日期：2024年11月1日修订日期：2024年11月29日接受日期：2024年12月4日发布日期：2024年12月12日OI：https://doi.org/10.1038/s10038-024-01311-zShare本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供