1 research outputs found
Somatic mosaicism by a de novo MLH1 mutation as a cause of Lynch syndrome
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