Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome DOI Creative Commons

Klaudia Horti-Oravecz,

Anikó Bozsik,

Tímea Pócza

et al.

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 18, 2025

Abstract Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with suspicion LS where MGPT no LS-related PV. Among 100 enrolled patients, 28 simple PVs an additional 3 complex PVs. 69 MGPT-negative lack somatic MLH1 promoter methylation in patient distinguished allelic imbalance selected this sample WGS. This returned germline deep intronic variant, further functional studies confirming its’ pathogenicity. Interestingly, all three PV were found to recurrent at our center. Our straightforward cost-effective optimally include genetic LS.

Language: Английский

Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome DOI Creative Commons

Klaudia Horti-Oravecz,

Anikó Bozsik,

Tímea Pócza

et al.

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 18, 2025

Abstract Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with suspicion LS where MGPT no LS-related PV. Among 100 enrolled patients, 28 simple PVs an additional 3 complex PVs. 69 MGPT-negative lack somatic MLH1 promoter methylation in patient distinguished allelic imbalance selected this sample WGS. This returned germline deep intronic variant, further functional studies confirming its’ pathogenicity. Interestingly, all three PV were found to recurrent at our center. Our straightforward cost-effective optimally include genetic LS.

Language: Английский

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