Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening

Juhari, Wan Khairunnisa Wan; Rahman, Wan Faiziah Wan Abdul; Sidek, Ahmad Shanwani Mohd; Hassan, Muhammad Radzi Abu; Noordin, Khairul Bariah Ahmad Amin; Zakaria, Andee Dzulkarnaen; Macrae, Finlay; Zilfalil, Bin Alwi

doi:10.7314/apjcp.2015.16.9.3767

Cited by 4 publications

(3 citation statements)

References 13 publications

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“…Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded (FFPE) tissue from a biopsy or resected bowel specimen. Immunohistochemical staining using four types of MMR antibodies—MLH1, MSH2, MSH6, and PMS2—and semi-quantitative scoring assessment were performed, as described previously by our groups [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Whole-Genome Profiles of Malay Colorectal Cancer Patients with Intact MMR Proteins

Juhari

Noordin

Zakaria

et al. 2021

Genes

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Background: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression. Method: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms. Results: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes—IFNE, PTCH2 and SEMA3D—which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes—ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117—harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway. Conclusion: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.

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Section: Methodsmentioning

confidence: 99%

Whole-Genome Profiles of Malay Colorectal Cancer Patients with Intact MMR Proteins

Juhari

Noordin

Zakaria

et al. 2021

Genes

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“…14 In Malaysia, the revised Bethesda criteria that assesses the pedigree, has been used in several studies of HNPCC as the criteria for patient' selection. 22,26 To date, there are almost 14,800 known different germline mutations for HNPCC, with many published in the International Society of Gastrointestinal Hereditary Tumours (InSiGHT) database (http:// www.insight-group.org/). There has been no published study examining HNPCC familial mutations specific to the Malay population, which is the biggest ethnic group in Malaysia.…”

Section: Hereditarymentioning

confidence: 99%

“…c.211+9C>G. We previously reported no loss of expression in patients carrying the variants as evidenced by immunohistochemical staining. 22 Only immunohistochemical staining on patient F22.…”

Section: Screening Of Germline Mutations and Polymorphisms In Mlh1 Anmentioning

confidence: 99%

MLH1 and MSH2 Gene Mutations and Polymorphisms in Six Malay Families with Hereditary Nonpolyposis Colorectal Cancer

Juhari¹,

Noordin²,

Rahman³

et al. 2018

imjm

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Background: Hereditary nonpolyposis colorectal cancer (HNPCC) also known as Lynch syndrome is commonly caused by genetic alterations in any of the four mismatch repair (MMR) genes; MLH1, MSH2, MSH6 and PMS2. This is the first study aimed to investigate genetic variants in Malay HNPCC families. Methods: Six Malay HNPCC families who fulfilled any of the Bethesda criteria were recruited into this study. A total of 3 ml of blood was withdrawn from each patient in the families. The samples were further analyzed using polymerase chain reaction and direct sequencing of the selected exons of MLH1 and MSH2 genes. Results: Two missense mutations and four single nucleotide polymorphisms (SNPs) were identified in six patients. These variants in the MLH1 and MSH2 genes were identified in four families who met the revised Bethesda guidelines. In two families, no mutation and polymorphism was identified in both the exon and intron of the respective genes. Of the mutations and polymorphisms identified, five have never been reported in Malay HNPCC families before. A missense mutation was detected in exon 5 of the MLH1 gene, c.394G>C (p.Asp132His) and four mutations and polymorphisms were detected in the MSH2 gene; heterozygous c.211+98T>C and c.211+9C>G and homozygous c.211+98T>C and c.211+9C>G, c.367-86A>C and c.382C>G. Conclusion: The results represented a new spectrum of mutations and polymorphisms in the Malay HNPCC families. However, a larger study involving additional families and analysis is required to determine the impact and nature of the identified mutations and polymorphisms.

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MLH1 and MSH2 mismatch repair protein profile using immunohistochemistry in Nepalese colorectal cancer patients

et al. 2020

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BACKGROUND Hereditary nonpolyposis colorectal cancer, or Lynch syndrome, caused by germline mutations or genetic defects in mismatch repair (MMR) genes (MLH1, MSH2, PMS2, MSH6, and epithelial cellular adhesion molecule), is an autosomal dominant condition accounting for 2–5% of all colorectal carcinomas (CRCs). Reports on MMR loss in many populations are available; however, there are no reports on the frequency of MMR protein expression in Nepalese cohorts. Therefore, this study was aimed to assess the expression profiles of MLH1 and MSH2 protein by immunohistochemistry (IHC) in Nepalese CRC patients. METHODS This retrospective study used archived formalin-fixed paraffin-embedded tissue blocks from 43 Nepalese CRC patients. IHC staining was performed using MLH1 and MSH2 antibodies. IHC scoring analysis was assessed using semiquantitative scoring. RESULTS Of the 43 CRC patients, 8 (18.6%) showed loss of staining for MLH1 antibody, 5 (11.6%) showed loss of staining for MSH2 antibody, and 4 (9.3%) showed loss of staining for both MLH1 and MSH2 antibodies. CONCLUSIONS IHC is a potential screening method of determining the MMR expression profile of Nepalese CRC patients. IHC can be performed in local clinical laboratories to find MMR protein defects in selected cases prior to expensive molecular tests.

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Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening

Cited by 4 publications

References 13 publications

Whole-Genome Profiles of Malay Colorectal Cancer Patients with Intact MMR Proteins

Whole-Genome Profiles of Malay Colorectal Cancer Patients with Intact MMR Proteins

MLH1 and MSH2 Gene Mutations and Polymorphisms in Six Malay Families with Hereditary Nonpolyposis Colorectal Cancer

MLH1 and MSH2 mismatch repair protein profile using immunohistochemistry in Nepalese colorectal cancer patients

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