Weber-Lassalle, Konstantin, Harter, Philipp, Hauke, Jan, Ernst, Corinna, Kommoss, Stefan, Marme, Frederik, Weber-Lassalle, Nana, Prieske, Katharina, Dietrich, Dimo, Borde, Julika, Pohl-Rescigno, Esther, Reuss, Alexander, Ataseven, Beyhan, Engel, Christoph ORCID: 0000-0002-7247-282X, Stingl, Julia C. ORCID: 0000-0002-1566-8156, Schmutzler, Rita K. and Hahnen, Eric (2018). Diagnosis of Li-Fraumeni Syndrome: Differentiating TP53 germline mutations from clonal hematopoiesis Results of the observational AGO-TR1 trial. Hum. Mutat., 39 (12). S. 2040 - 2047. HOBOKEN: WILEY. ISSN 1098-1004

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Abstract

The Li-Fraumeni cancer predisposition syndrome (LFS1) presents with a variety of tumor types and the TP53 gene is covered by most diagnostic cancer gene panels. We demonstrate that deleterious TP53 variants identified in blood-derived DNA of 523 patients with ovarian cancer (AGO-TR1 trial) were not causal for the patients' ovarian cancer in three out of six TP53-positive cases. In three out of six patients, deleterious TP53 mutations were identified with low variant fractions in blood-derived DNA but not in the tumor of the patient seeking advice. The analysis of the TP53 and PPM1D genes, both intimately involved in chemotherapy-induced and/or age-related clonal hematopoiesis (CH), in 523 patients and 1,053 age-matched female control individuals revealed that CH represents a frequent event following chemotherapy, affecting 26 of the 523 patients enrolled (5.0%). Considering that TP53 mutations may arise from chemotherapy-induced CH, our findings help to avoid false-positive genetic diagnoses of LFS1.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Weber-Lassalle, KonstantinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harter, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauke, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ernst, CorinnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kommoss, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marme, FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber-Lassalle, NanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prieske, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dietrich, DimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borde, JulikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pohl-Rescigno, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reuss, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ataseven, BeyhanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engel, ChristophUNSPECIFIEDorcid.org/0000-0002-7247-282XUNSPECIFIED
Stingl, Julia C.UNSPECIFIEDorcid.org/0000-0002-1566-8156UNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahnen, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-163855
DOI: 10.1002/humu.23653
Journal or Publication Title: Hum. Mutat.
Volume: 39
Number: 12
Page Range: S. 2040 - 2047
Date: 2018
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1098-1004
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FRAMEWORK; CANCERS; BLOOD; PPM1DMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16385

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