Misidentification of transthyretin and immunoglobulin variants by proteomics due to methyl lysine formation in formalin-fixed paraffin-embedded amyloid tissue
| Autor: | Dorota Rowczenio, Graham W. Taylor, Sara Motta, Lucia Di Vagno, Janet A. Gilbertson, Pierluigi Mauri, Phillip N. Hawkins, Nigel B. Rendell, Tamar Rezk, Palma Mangione, Diana Canetti, Sofia Giorgetti, Antonella De Palma, Guglielmo Verona, Vittorio Bellotti, Julian D. Gillmore |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Proteomics 0301 basic medicine Amyloid Lysine Mutation Missense Peptide 03 medical and health sciences 0302 clinical medicine Immunoglobulin lambda-Chains Formaldehyde Internal Medicine medicine Humans Prealbumin Amyloidosis formalin immunoglobulin proteomics transthyretin variant Aged Aged 80 and over chemistry.chemical_classification Paraffin Embedding biology Methylation Middle Aged medicine.disease Molecular biology Transthyretin 030104 developmental biology Amino Acid Substitution chemistry Biochemistry 030220 oncology & carcinogenesis biology.protein Female Antibody |
| Zdroj: | Amyloid (Carnforth) (2017): 1–9. doi:10.1080/13506129.2017.1385452 info:cnr-pdr/source/autori:Canetti, Diana; Rendell, Nigel Brian; Di Vagno, Lucia; Gilbertson, Janet A; Rowczenio, Dorota; Rezk, Tamar; Gillmore, Julian D; Hawkins, Phillip N; Verona, Guglielmo; Mangione, Palma Patrizia; Giorgetti, Sofia; Mauri, Pierluigi; Motta, Sara; De Palma, Antonella; Bellotti, Vittorio; Taylor, Graham W/titolo:Misidentification of transthyretin and immunoglobulin variants by proteomics due to methyl lysine formation in formalin-fixed paraffin-embedded amyloid tissue./doi:10.1080%2F13506129.2017.1385452/rivista:Amyloid (Carnforth)/anno:2017/pagina_da:1/pagina_a:9/intervallo_pagine:1–9/volume |
| ISSN: | 1744-2818 1350-6129 |
| Popis: | Proteomics is becoming the de facto gold standard for identifying amyloid proteins and is now used routinely in a number of centres. The technique is compound class independent and offers the added ability to identify variant and modified proteins. We re-examined proteomics results from a number of formalin-fixed paraffin-embedded amyloid samples, which were positive for transthyretin (TTR) by immunohistochemistry and proteomics, using the UniProt human protein database modified to include TTR variants. The amyloidogenic variant, V122I TTR, was incorrectly identified in 26/27 wild-type and non-V122I variant samples due to its close mass spectral similarity with the methyl lysine-modified WT peptide [126KMe]105–127 (p.[146 KMe]125–147) generated during formalin fixation. Similarly, the methyl lysine peptide, [50KMe]43–59, from immunoglobulin lambda light chain constant region was also misidentified as arising from a rare myeloma-derived lambda variant V49I. These processing-derived modifications are not present in fresh cardiac tissue, non-fixed fat nor serum and do not materially affect the identification of amyloid proteins. They could result in the incorrect assignment of a variant, and this may have consequences for the immediate family who will require genetic counselling and potentially early clinical intervention. As proteomics becomes a routine clinical test for amyloidosis, it becomes important to be aware of potentially confounding issues such as formalin-mediated lysine methylation, and how these may influence diagnosis and possibly treatment. |
| Databáze: | OpenAIRE |
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