Increased Prevalence of Germline Pathogenic CHEK2 Variants in Individuals With Pituitary Adenomas
Authors' conclusion
This is the first study to suggest a role for the breast cancer predisposition gene, CHEK2, in pituitary tumorigenesis, with pathogenic/likely pathogenic variants found in 3% of patients with PAs. As PAs are relatively common and typically lack classic autosomal dominant family histories, risk alleles-such as these variants found in CHEK2-might be a significant contributor to PA risk in the general population.
Study context
- Population
- Individuals with pituitary adenomas; primary cohort with germline and tumor whole-exome sequencing, second cohort with targeted next-generation sequencing panel (germline and tumor DNA n = 52, germline DNA alone n = 84)2 cohorts (29 + 136)
- Participants
- 165 individuals
- Exposure
- PA cohort vs national control data
- PAn = 165
- Outcome
- Rate and pathogenicity of CHEK2 variants
Methodological detailsgermline and tumor sequencing, primary cohort and independent second cohort
- Germline and tumor sequencing
- Primary cohort and independent second cohort
Main finding
As reported in the abstract
Rare, coding, nonsynonymous germline CHEK2 variants
PA
3.0%
5 of 165
- Primary cohort: 3 of 29
- 10.3%
- Pathogenic definitive null variants (c.1100delC, c.444 + 1G > A)
- 2
- Likely pathogenic missense variants (p.Asn186His, p.Thr476Met)
- 2
Observational data: associations, not effects.
Further findings
Null CHEK2 variants only · higher in PA cohort
P = 0.049
Original publication
Increased Prevalence of Germline Pathogenic CHEK2 Variants in Individuals With Pituitary Adenomas. J Clin Endocrinol Metab. Published 23 April 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →