RT Journal Article
SR Electronic
T1 N_LyST: a simple and rapid screening test for Lynch syndrome
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 713
OP 720
DO 10.1136/jclinpath-2018-205013
VO 71
IS 8
A1 Susanti, Susanti
A1 Fadhil, Wakkas
A1 Ebili, Henry Okuchukwu
A1 Asiri, Abutaleb
A1 Nestarenkaite, Ausrine
A1 Hadjimichael, Efthymios
A1 Ham-Karim, Hersh A
A1 Field, Joanne
A1 Stafford, Katherine
A1 Matharoo-Ball, Balwir
A1 Hassall, James C
A1 Sharif, Abid
A1 Oniscu, Anca
A1 Ilyas, Mohammad
YR 2018
UL http://jcp.bmj.com/content/71/8/713.abstract
AB Aims We sought to use PCR followed by high-resolution melting analysis to develop a single closed-tube screening panel to screen for Lynch syndrome. This comprises tests for microsatellite instability (MSI), MLH1 methylation promoter and BRAF mutation.Methods For MSI testing, five mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1) were developed. In addition, primers were designed to interrogate Region C of the MLH1 promoter for methylation (using bisulphite-modified DNA) and to test for mutations in codon 600 of BRAF. Two separate cohorts from Nottingham (n=99, 46 with MSI, 53 being microsatellite stable (MSS)) and Edinburgh (n=88, 45 MSI, 43 MSS) were tested.Results All the cases (n=187) were blind tested for MSI and all were correctly characterised by our panel. The MLH1 promoter and BRAF were tested only in the Nottingham cohort. Successful blinded analysis was performed on the MLH1 promoter in 97 cases. All MSS cases showed a pattern of non-methylation while 41/44 cases with MSI showed full methylation. The three cases with MSI and a non-methylated pattern had aberrations in MSH2 and MSH6 expression. BRAF mutation was detected in 61% of MSI cases and 11% of MSS cases.Finally, 12 cases were blind screened by using the whole panel as a single test. Of these, five were identified as MSS, four as MSI/non-LS and three as MSI/possible LS. These results were concordant with the previous data.Conclusion We describe the Nottingham Lynch Syndrome Test (N_LyST). This is a quick, simple and cheap method for screening for Lynch syndrome.