Genotype-phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry

被引：10

作者：

Penkert, Judith ^{[1
,2
]}

Struewe, Farina J. ^{[1
]}

Dutzmann, Christina M. ^{[1
]}

Doergeloh, Beate B. ^{[1
]}

Montellier, Emilie ^{[3
]}

Freycon, Claire ^{[3
,4
]}

Keymling, Myriam ^{[5
]}

Schlemmer, Heinz-Peter ^{[5
]}

Saenger, Birte ^{[1
]}

Hoffmann, Beatrice ^{[1
]}

Gerasimov, Tanja ^{[1
]}

Blattmann, Claudia ^{[6
]}

Fetscher, Sebastian ^{[7
]}

Fruhwald, Michael ^{[8
]}

Hettmer, Simone ^{[9
]}

Kordes, Uwe ^{[10
]}

Ridola, Vita ^{[11
]}

Kroiss Benninger, Sabine ^{[12
]}

Mastronuzzi, Angela ^{[13
]}

Schott, Sarah ^{[14
]}

Nees, Juliane ^{[14
]}

Prokop, Aram ^{[15
,16
,17
]}

Redlich, Antje ^{[18
]}

Seidel, Markus G. ^{[19
]}

Zimmermann, Stefanie ^{[20
]}

Pajtler, Kristian W. ^{[21
,22
,23
,24
]}

Pfister, Stefan M. ^{[21
,22
,23
,24
]}

Hainaut, Pierre ^{[3
]}

Kratz, Christian P. ^{[1
]}

机构：

[1] Hannover Med Sch, Pediat Hematol & Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany

[2] Hannover Med Sch, Dept Human Genet, Hannover, Germany

[3] Univ Grenoble Alpes, Inserm 1209, CNRS 5309, Inst Adv Biosci, F-38000 Grenoble, France

[4] Grenoble Alpes Univ Hosp, Dept Pediat, Grenoble, France

[5] German Canc Res Ctr, Div Radiol, Heidelberg, Germany

[6] Klinikum Stuttgart, Dept Pediat Oncol Hematol & Immunol, Olgahosp, Stuttgart, Germany

[7] Sana Hosp, Dept Haematol & Oncol, Lubeck, Germany

[8] Univ Med Ctr Augsburg, Paediat & Adolescent Med, Augsburg, Germany

[9] Univ Freiburg, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, Univ Med Ctr Freiburg, Freiburg, Germany

[10] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany

[11] MITERA Childrens Hosp, Dept Pediat Oncol & Hematol, Athens, Greece

[12] Univ Childrens Hosp Zurich, Dept Oncol, Zurich, Switzerland

[13] IRCCS Bambino Gesu Childrens Hosp, Dept Haematol Oncol Cell Therapy Gene Therapies &, Rome, Italy

[14] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany

[15] Helios Clin Schwerin, Dept Pediat Hematol Oncol, Schwerin, Germany

[16] Univ Appl Sci & Med Univ, Med Sch Hamburg MSH, Hamburg, Germany

[17] Childrens Hosp, Dept Pediat Hematol & Oncol, Cologne, Germany

[18] Otto von Guericke Univ Childrens Hosp, Pediat Oncol Dept, Magdeburg, Germany

[19] Med Univ Graz, Dept Pediat & Adolescent Med, Div Pediat Hematol Oncol, Graz, Austria

[20] Univ Hosp, Pediat Hematol & Oncol, Frankfurt, Germany

[21] Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany

[22] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany

[23] German Canc Consortium DKTK, Heidelberg, Germany

[24] Heidelberg Univ Hosp, Dept Pediat Hematol & Oncol, Heidelberg, Germany

来源：

JOURNAL OF HEMATOLOGY & ONCOLOGY | 2022年 / 15卷 / 01期

关键词：

Li-Fraumeni syndrome; TP53; Genotype; Phenotype; Cancer predisposition; CANCER;

D O I：

10.1186/s13045-022-01332-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype-phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS (P value < 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value < 0.01). Our study suggests genotype-phenotype correlations encouraging further analyses.

引用

页数：5

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