Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia

There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016–2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all—186/197 (99.45%)—MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as “Probable Lynch” (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%, p = 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both “Probable Lynch” and non-LS (sporadic) groups (n = 227) was comparable (p = 0.59), with follow up period of 0–1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (p < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72–11.2; p = 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.

Isotypies for the quasisimple groups with exceptional Schur multiplier

Let [Formula: see text] be a block with abelian defect group [Formula: see text] of a quasisimple group [Formula: see text], such that [Formula: see text] has exceptional Schur multiplier. We show that, [Formula: see text] is isotypic to its Brauer correspondent in [Formula: see text] in the sense of Broué. The proof uses methods from a previous paper [B. Sambale, Broué’s isotypy conjecture for the sporadic groups and their covers and automorphism groups, Internat. J. Algebra Comput. 25 (2015) 951–976], and relies ultimately on computer calculations. Moreover, we verify the Alperin–McKay conjecture for all blocks of [Formula: see text].

Broué's isotypy conjecture for the sporadic groups and their covers and automorphism groups

Let B be a p-block of a finite group G with abelian defect group D such that S ≤ G ≤ Aut (S), S′ = S and S/Z(S) is a sporadic simple group. We show that B is isotypic to its Brauer correspondent in N G(D) in the sense of Broué. This has been done by Rouquier for principal blocks and it remains to deal with the non-principal blocks.