Pathology update to the Manchester Scoring System based on testing in over 4000 families. - PubMed - NCBI
J Med Genet. 2017 May 10. pii: jmedgenet-2017-104584. doi: 10.1136/jmedgenet-2017-104584. [Epub ahead of print]
Pathology update to the Manchester Scoring System based on testing in over 4000 families.
Evans DG1,2,3,4,5,
Harkness EF6,
Plaskocinska I7,
Wallace AJ3,
Clancy T3,
Woodward ER1,3,
Howell TA2,5,
Tischkowitz M7,
Lalloo F3.
Abstract
BACKGROUND:
While the requirement for thresholds for testing for mutations in BRCA1/2 is being questioned, they are likely to remain for individuals unaffected by a relevant cancer. It is still useful to provide pretesting likelihoods, but models need to take into account tumour pathology. METHODS:
The Manchester Scoring System (MSS) is a well-used, simple, paper-based model for assessing carrier probability that already incorporates pathology data. We have used mutation testing data from 4115 unrelated samples from affected non-Jewish individuals alongside tumour pathology to further refine the scoring system. RESULTS:
Adding additional points for high-grade serous ovarian cancer <60 (HGSOC=+2) and adding grade score to those with triple-negative breast cancer, while reducing the score for those with HER2+ breast cancer (-6), resulted in significantly improved sensitivity and minor improvements in specificity to the MSS. Sporadic HGSOC <60 years thus reached a score of 15-19 points within the 10% grouping consistent with the 15/113-13.2% that were identified with a BRCA1/2 pathogenic variant. Validation in a population series of ovarian cancer from Cambridge showed high sensitivity at the 10% threshold 15/17 (88.2%). CONCLUSIONS:
The new pathology-adjusted Manchester score MSS3 appears to provide an effective and simple-to-use estimate of the 10% and 20% thresholds for BRCA1/2 likelihood. For unaffected individuals, the 20-point (20%) threshold in their affected first-degree relative can be used to determine eligibility at the 10% threshold. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
KEYWORDS:
BRCA1; BRCA2; Manchester Scoring System; high grade serous ovarian cancer; pathology; triple negative breast cancer
.png)
No hay comentarios:
Publicar un comentario