Ask about this productRelated genes to: MLH1 antibody
- Gene:
- MLH1 NIH gene
- Name:
- mutL homolog 1
- Previous symbol:
- COCA2
- Synonyms:
- HNPCC, FCC2, HNPCC2
- Chromosome:
- 3p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-11-24
- Date modifiied:
- 2019-04-23
Related products to: MLH1 antibody
Related articles to: MLH1 antibody
- Sebaceous adenoma is a rare benign sebaceous neoplasm that only exceptionally involves the ocular adnexa. Caruncular lesions are particularly uncommon and often resemble more frequently encountered lesions such as papilloma. Correct diagnosis of these tumours is important because sebaceous neoplasms may be associated with Muir-Torre syndrome (MTS), a hereditary cancer predisposition syndrome within the Lynch syndrome spectrum. Modern pathology reports incorporate mismatch repair (MMR) immunohistochemistry to help identify patients who may require genetic assessment and cancer surveillance. We present the case of an 81-year-old woman who presented with a right caruncular lesion associated with epiphora and mucoid discharge. Clinical examination demonstrated a cream coloured papillomatous lesion that was mobile and not adherent to adjacent structures. The lesion was presumed clinically to represent a benign papilloma and was excised during combined lacrimal surgery. Histopathological examination demonstrated a well-circumscribed lobulated sebaceous proliferation composed predominantly of mature sebocytes with peripheral basaloid germinative cells and no significant atypia, consistent with sebaceous adenoma. Immunohistochemistry demonstrated preserved nuclear expression of MutL Homologue 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homologue 2 (MSH2) and MutS homologue 6 (MSH6), indicating intact MMR function and reducing suspicion for MTS. Sebaceous adenoma should be considered in the differential diagnosis of cream-white papillomatous caruncular lesions. Ophthalmologists should understand the significance of MMR immunohistochemistry, as abnormal results may identify patients requiring genetic referral, whereas preserved expression is generally reassuring and supports a sporadic lesion. Retained nuclear staining for MLH1, PMS2, MSH2 and MSH6 indicated preserved MMR function (MMR proficient; pMMR), which predicts microsatellite stability (MSS). In conjunction with the patient's age and absence of a personal history of malignancy, these findings strongly favoured a sporadic sebaceous adenoma. Although intact MMR expression does not completely exclude MTS, abnormal staining would have prompted consideration of genetic referral and systemic evaluation. Our report expands upon previous literature by providing a practical explanation of MMR immunohistochemistry aimed at ophthalmologists, who may be the first clinicians to recognise sebaceous neoplasia and initiate appropriate MTS screening. - Source: PubMed
Publication date: 2026/07/22
Cheung ImogenCheung David - Huntington's disease (HD) is a life-altering genetic neurodegenerative disorder, with cognitive, motor, and psycho-social effects that have consequential impacts on the individuals and their families. While current treatments improve disease symptoms, there are no FDA-approved therapies that prevent disease progression. Converging lines of evidence from human GWAS and mouse models point to DNA repair and handling (R/H) proteins as promising therapeutic targets due to their ability to modulate somatic expansion of the CAG repeat of HTT. The roles of DNA R/H HD modulator proteins are incompletely understood, in part, due to their relatively low cellular abundance and technical challenges in quantification. Here, we developed and validated targeted mass spectrometry assays quantifying DNA R/H proteins, spanning functions in mismatch repair, Fanconi anemia, and transcriptional regulation, using complementary workflows for timsTOF and Orbitrap platforms. We built species-specific experiment spectral libraries that outperformed in silico libraries for target detection. Applying this pipeline to an HTT-Q140 knock-in mouse HD model, we observed that DNA R/H protein abundances were largely unchanged in HD mice, while HTT and HAP40 showed increased nuclear association with disease progression. To facilitate translational research applications, we further developed a stable isotope dilution assay for absolute quantification of 11 human mismatch repair-associated proteins and generated an HTT knock-out human neuroblastoma cell line. Additionally, we used thermal proximity coaggregation profiling to characterize the endogenous interactomes of MMR proteins. We observed that HTT KO caused proteome down-regulation in selected DNA R/H proteins and reshaped the MMR protein interactome, with the most pronounced changes observed for MLH1 and PMS1 interactions. Overall, we established a validated, transferable assay for quantifying DNA R/H proteins in perturbation studies using human and mouse HD model systems and provide evidence that HTT influences the abundance and interaction landscape of proteins central to CAG repeat instability. - Source: PubMed
Publication date: 2026/07/29
Greco Todd MHutton Josiah EJustice Joshua LReed Tavis JVogt Thomas FPrasad Brinda CCristea Ileana M - Deficiency in SWItch/Sucrose Non-FermenTable (SWI/SNF) related barrier-to-autointegration factor (BAF) chromatin remodeling complex subunit ATPase 4 (SMARCA4) drives aggressive behavior across various undifferentiated malignancies. However, its clinicopathological features, prognostic analysis, and molecular significance in undifferentiated digestive system malignancies, clinically rare and poorly characterized entities, remain incompletely elucidated. This study investigated the clinicopathological characteristics and prognostic significance of a retrospective cohort (n = 43). Immunohistochemistry (IHC) identified SMARCA4 deficiency in 30.2% of undifferentiated malignant tumors of the digestive system. Clinically, SMARCA4 deficiency constituted a significant poor-prognosis predictor, correlating with poorer overall survival [OS; hazard ratio (HR) = 3.054, 95% confidence interval (CI) 1.277-7.306, log-rank p = 0.006] and disease-free survival (DFS; HR = 2.717, 95% CI 1.129-6.539, log-rank p = 0.015), independent of assessed lineage markers or microsatellite status. Integrated analysis of The Cancer Genome Atlas (TCGA) data of digestive system malignancies revealed that SMARCA4-mutated tumors exhibited elevated tumor mutational burden (TMB) and distinct co-mutation patterns. Notably, SMARCA4 mutations significantly co-occurred with multiple potentially actionable therapeutic targets, including receptor tyrosine kinases (ERBB2, ERBB3, MET, and RET), DNA damage response genes (BRCA2), and mismatch repair genes (MLH1, MSH2, MSH6). Collectively, our findings identified SMARCA4 deficiency as a predictor of poor prognoses in digestive system malignancies, suggesting a distinct genomic context that may inform therapeutic stratification, including targeted and immunotherapeutic approaches, by focusing on these high-frequency co-mutated targets. © 2026 The Pathological Society of Great Britain and Ireland. - Source: PubMed
Publication date: 2026/08/20
Guo Yun-RanLiu ChangBai XiaoLi Ke-ChenZhao Jia-BaoLin KunZhao Zi-TingLang Ji-XuanLi Xiao-HanWu Qi-JunZhang Chun-Dong - Identifying hereditary colorectal cancer genes is historically complicated by genetic heterogeneity. Founder populations simplify genetic architecture through reduced allelic diversity and extended linkage disequilibrium. This write-up explores how Finland's unique demographic history, driven by geographic isolation and severe population bottlenecks, established the distinct "Finnish disease heritage." In the 1990s, this regional homogeneity proved instrumental in successfully mapping recurrent germline MLH1 (MutL Homolog 1) founder mutations in Lynch syndrome. - Source: PubMed
Publication date: 2026/08/11
Rajaram Nirmal RajKaur Paramjot - DNA mismatch repair (MMR) deficiency is a clinically important biomarker in human oncology, yet its relevance in feline neoplasia remains poorly understood due to limited characterisation and the absence of validated reagents. In this study, we established a practical immunohistochemistry (IHC) approach for evaluating feline MMR proteins by confirming the cross-reactivity of anti-human MLH1, MSH2 and MSH6 antibodies using CRISPR/Cas9-engineered feline tumour cell lines lacking each target gene. Using these validated antibodies, we conducted a pilot screening to assess MMR protein expression in 83 feline tumours and observed variable reductions or losses of MLH1, MSH2 and MSH6 across several tumour types. Notably, MLH1 expression was lost in all melanoma cases (6/6, 100%) and in most osteosarcomas (14/15, 93%), indicating that MMR perturbations may be particularly relevant in these malignancies. These findings provide the first analytically validated framework for assessing MMR proteins in feline oncology and suggest that MMR dysregulation may be more widespread than previously recognised. Although the clinical sample size is limited, this initial pilot screening maps the preliminary landscape of feline MMR protein expression. Further large-scale validation studies incorporating microsatellite instability testing, methylation analysis and genomic profiling are warranted to clarify the biological significance of these alterations. - Source: PubMed
Publication date: 2026/08/16
Nishibori ShomaSakurai MasashiKagawa YumikoNishigaki KazuoNakagawa TakayukiInanaga SakuyaIgase MasayaMizuno Takuya