Anti - Mouse, MLH1 Clone ZM001
- Known as:
- Anti - Mouse, MLH1 Clone ZM001
- Catalog number:
- 60-0075-7
- Product Quantity:
- 7mL
- Category:
- -
- Supplier:
- Genemed
- Gene target:
- Anti - Mouse MLH1 Clone ZM001
Related genes to: Anti - Mouse, MLH1 Clone ZM001
- 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: Anti - Mouse, MLH1 Clone ZM001
Related articles to: Anti - Mouse, MLH1 Clone ZM001
- The identification of a pathogenic variant (PV) in one of the mismatch repair (MMR) genes confirms the diagnosis of Lynch syndrome (LS). Hence, the correct classification of MMR gene variants is of utmost importance for appropriate counselling, surveillance, and treatment of LS patients and their families. In 7/200 unrelated Tyrolean-suspected LS patients, we identified the rare variant :c.836T>G. Clinical and tumor data strongly indicate that this founder variant is associated with an increased risk for early-onset LS-associated tumors. We also demonstrate that the variant leads to aberrant mRNA splicing. However, the splice effect's leakiness together with the small effect of the amino acid change p.(Val297Gly) encoded by the residual full-length transcripts in a functional assay preclude its formal classification as (likely) PV according to internationally accepted variant interpretation guidelines. The family histories of the carriers suggest that the obstacles to classify the variant as (likely) PV may be related with a reduced penetrance. Nonetheless, and despite the formal classification of :c.836T>G as a variant of uncertain significance, we show that carriers should undergo cancer surveillance and predictive testing should be offered to relatives. This variant illustrates the need for an improved classification framework for appropriate categorization of lower-penetrance alleles. - Source: PubMed
Publication date: 2026/08/17
Horpaopan SukanyaSchamschula EstherFiegl HeidelindeDapoz HannesLutz-Nicoladoni ChristinaSchnaiter SimonAmberger AlbertStrasser UlrichLunzer Renatevon der Heidt AndreasCsanaky KatalinZschocke JohannesWimmer Katharina - : Mismatch repair deficiency (MMRd) is a central molecular determinant of colorectal cancer (CRC) biology, prognosis, and treatment response, and Universal Tumour Screening (UTS) is advocated for Lynch syndrome (LS) detection; yet real-world performance across clinical subgroups remains limited. We evaluated MMRd distribution and UTS-based LS detection in a large consecutive surgical cohort. : We retrospectively analyzed 1022 consecutive CRC patients undergoing surgical resection at the University Hospital of Padua (2015-2023). MMR status was assessed by immunohistochemistry; MMRd cases underwent reflex BRAF mutation testing and, when available, MLH1 promoter methylation analysis, followed by germline multigene panel testing for suspected LS. Clinicopathological features were compared by MMR status, age at onset, and tumour location. : MMR testing was performed in 875 patients (85.6%), rising from 67.0% (2015-2017) to 97.4% (2021-2023). MMRd was identified in 139 tumors (15.9%) and was independently associated with age ≥ 70 years, colonic location, and stage 0-II. Of 22 patients with confirmed LS, 13 (59.1%) were newly identified through UTS; family history showed no significant univariate association with LS status and was not independently associated with MMRd after multivariable adjustment. MMRd prevalence was numerically higher in early- than late-onset CRC (20.0% vs. 15.4%), approaching significance after multivariable adjustment (OR 1.90, 95% CI 0.99-3.64; = 0.054); hereditary syndromes were also more frequent in early-onset disease. MMRd was markedly rarer in rectal than colonic cancer (4.1% vs. 22.5%; < 0.0001), though MMRd rectal cancers arose in younger patients. : UTS identified a substantial proportion of LS carriers missed by age- or family-history criteria. The relationship between age and MMRd prevalence proved more nuanced than a simple comparison would suggest, reinforcing the value of universal over selective testing across the age spectrum, while MMRd rectal cancer shows a distinct younger profile relevant to immunotherapy-based organ preservation. - Source: PubMed
Publication date: 2026/08/08
Negro SilviaLessio SaraPasseri DanieleBaldo AndreaScarpa MarcoTos Angelo Paolo DeiPennelli GanmariaSchiavi FrancescaPinato ClaudiaFassan MatteoBao Quoc RiccardoBergamo FrancescaLonardi SaraSpolverato GayaUrso Emanuele Damiano Luca - Mismatch repair deficiency (MMRd) is a key determinant of tumour biology, however, its prognostic significance in patients with resectable oesophagogastric adenocarcinoma treated with perioperative cytotoxic chemotherapy remains uncertain. - Source: PubMed
Publication date: 2026/08/25
Ntellas PanagiotisLund TomKeogh Georgina ASalto-Tellez Manuelvon Loga KatharinaSilveira TatianyRiisnaes SusannaLaye JonLangley Ruth ENankivell Matthew GAllum William HAthauda AvaniCunningham DavidGrabsch Heike I - 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