eprintid: 10024837
rev_number: 36
eprint_status: archive
userid: 608
dir: disk0/10/02/48/37
datestamp: 2017-10-17 11:17:40
lastmod: 2021-09-30 22:43:49
status_changed: 2017-10-17 11:17:40
type: article
metadata_visibility: show
creators_name: Canetti, D
creators_name: Rendell, NB
creators_name: Di Vagno, L
creators_name: Gilbertson, JA
creators_name: Rowczenio, D
creators_name: Rezk, T
creators_name: Gillmore, JD
creators_name: Hawkins, PN
creators_name: Verona, G
creators_name: Mangione, PP
creators_name: Giorgetti, S
creators_name: Mauri, P
creators_name: Motta, S
creators_name: De Palma, A
creators_name: Bellotti, V
creators_name: Taylor, GW
title: Misidentification of transthyretin and immunoglobulin variants by proteomics due to methyl lysine formation in formalin-fixed paraffin-embedded amyloid tissue
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G90
divisions: G93
keywords: Amyloidosis, formalin, immunoglobulin, proteomics, transthyretin, variant
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: 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.
date: 2017
date_type: published
official_url: https://doi.org/10.1080/13506129.2017.1385452
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1434955
doi: 10.1080/13506129.2017.1385452
lyricists_name: Bellotti, Vittorio
lyricists_name: Canetti, Diana
lyricists_name: Gilbertson, Janet
lyricists_name: Gillmore, Julian
lyricists_name: Hawkins, Philip
lyricists_name: Mangione, Palma
lyricists_name: Rendell, Nigel
lyricists_name: Rezk, Tamer
lyricists_name: Rowczenio, Dorota
lyricists_name: Taylor, Graham
lyricists_name: Verona, Guglielmo
lyricists_id: VBELL78
lyricists_id: DCANE19
lyricists_id: JAGIL44
lyricists_id: JGILL78
lyricists_id: PNHAW77
lyricists_id: PMANG84
lyricists_id: NREND34
lyricists_id: TMIRE17
lyricists_id: DROWC07
lyricists_id: GTAYL13
lyricists_id: GVERO54
actors_name: Taylor, Graham
actors_id: GTAYL13
actors_role: owner
full_text_status: public
publication: Amyloid
volume: 27
number: 4
pagerange: 229-237
event_location: England
issn: 1744-2818
citation:        Canetti, D;    Rendell, NB;    Di Vagno, L;    Gilbertson, JA;    Rowczenio, D;    Rezk, T;    Gillmore, JD;                                     ... Taylor, GW; + view all <#>        Canetti, D;  Rendell, NB;  Di Vagno, L;  Gilbertson, JA;  Rowczenio, D;  Rezk, T;  Gillmore, JD;  Hawkins, PN;  Verona, G;  Mangione, PP;  Giorgetti, S;  Mauri, P;  Motta, S;  De Palma, A;  Bellotti, V;  Taylor, GW;   - view fewer <#>    (2017)    Misidentification of transthyretin and immunoglobulin variants by proteomics due to methyl lysine formation in formalin-fixed paraffin-embedded amyloid tissue.                   Amyloid , 27  (4)   pp. 229-237.    10.1080/13506129.2017.1385452 <https://doi.org/10.1080/13506129.2017.1385452>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10024837/1/N%3A%5CAAGWT%20WORKING%5CMANUSCRIPTS%5CMethyl%20lysine%20paper%20Mar%202017%5CMethyl%20lysine%20in%20formalin%20Amyloid%20Final%20UCL%20uploaded.pdf