Open AccessSomatic mosaicism by a de novo MLH1 mutation as a cause of Lynch syndrome
Author(s) -
GeurtsGiele Willemina R.,
Rosenberg Efraim H.,
Rens Anja van,
Leerdam Monique E. van,
Dinjens Winand N.,
Bleeker Fonnet E.
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.699
Subject(s) - lynch syndrome , mlh1 , germline mutation , genetics , mutation , somatic cell , dna mismatch repair , germline mosaicism , germline , pms2 , biology , medicine , cancer , cancer research , gene , colorectal cancer
Background Lynch syndrome (LS) is caused by germline mismatch repair (MMR) gene mutations. De novo MMR gene mutations are rare, and somatic mosaicism in LS is thought to be infrequent. We describe the first case of somatic mosaicism by a de novo MLH1 mutation for a patient diagnosed with a rectosigmoid adenocarcinoma at age 31. Methods Twelve years after initial colorectal cancer diagnosis, tumor tissue of the patient was tested with sensitive next generation sequencing (NGS) analysis for the presence of somatic MMR mutations. Results In tumor tissue, an inactivating MLH1 mutation (c.518_519del; p.(Tyr173Trpfs*18)) was detected, which was also present at low level in the blood of the patient. In both parents, as well as the patient's sisters, the mutation was not present. Conclusion We show that low‐level mosaicism can be detected by using high‐coverage targeted NGS panels on constitutional and/or tumor DNA. This report illustrates that by using sensitive sequencing techniques, more cases of genetic diseases driven by mosaic mutations may be identified, with important clinical consequences for patients and family members.