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L265P Mutation of the MYD88 Gene Is Frequent in Waldenström’s Macroglobulinemia and Its Absence in Myeloma

L265P mutation in the MYD88 gene has recently been reported in Waldenström’s macroglobulinemia; however the incidence has been different according to the methods used. To determine the relevance and compare the incidence by different methods, we analyzed the L265P mutation in bone marrow mononuclear...

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Autores principales: Mori, Naoki, Ohwashi, Mari, Yoshinaga, Kentaro, Mitsuhashi, Kenjiro, Tanaka, Norina, Teramura, Masanao, Okada, Michiko, Shiseki, Masayuki, Tanaka, Junji, Motoji, Toshiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818242/
https://www.ncbi.nlm.nih.gov/pubmed/24224040
http://dx.doi.org/10.1371/journal.pone.0080088
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author Mori, Naoki
Ohwashi, Mari
Yoshinaga, Kentaro
Mitsuhashi, Kenjiro
Tanaka, Norina
Teramura, Masanao
Okada, Michiko
Shiseki, Masayuki
Tanaka, Junji
Motoji, Toshiko
author_facet Mori, Naoki
Ohwashi, Mari
Yoshinaga, Kentaro
Mitsuhashi, Kenjiro
Tanaka, Norina
Teramura, Masanao
Okada, Michiko
Shiseki, Masayuki
Tanaka, Junji
Motoji, Toshiko
author_sort Mori, Naoki
collection PubMed
description L265P mutation in the MYD88 gene has recently been reported in Waldenström’s macroglobulinemia; however the incidence has been different according to the methods used. To determine the relevance and compare the incidence by different methods, we analyzed the L265P mutation in bone marrow mononuclear cells from lymphoid neoplasms. We first performed cloning and sequencing in 10 patients: 8 Waldenström’s macroglobulinemia; 1 non-IgM-secreting lymphoplasmacytic lymphoma; and 1 low grade B-cell lymphoma with monoclonal IgG protein. The L265P mutation was detected in only 1/8 Waldenström’s macroglobulinemia patients (2 of 9 clones). To confirm these results, direct sequencing was performed in the 10 patients and an additional 17 Waldenström’s macroglobulinemia patients and 1 lymphoplasmacytic lymphoma patient. Nine of 28 patients (7/25 Waldenström’s macroglobulinemia, 1/2 lymphoplasmacytic lymphoma, and B-cell lymphoma) harbored the mutation. We next tested for the mutation with BSiE1 digestion and allele-specific polymerase chain reaction in the 28 patients and 38 patients with myeloma. Aberrant bands corresponding to the mutation were detected by BSiE1 digestion in 19/25 patients with Waldenström’s macroglobulinemia (76%), 1/2 lymphoplasmacytic lymphoma and B-cell lymphoma, but not in the 38 myeloma patients. The L265P mutation was more frequent in patients with Waldenström’s macroglobulinemia than in those with myeloma (p=1.3x10(-10)). The mutation was detected by allele-specific polymerase chain reaction in 18/25 Waldenström’s macroglobulinemia patients (72%). In the 25 Waldenström’s macroglobulinemia patients, the L265P was more frequently detected by BSiE1 digestion than by direct sequencing (p=5.3x10(-4)), and in males (15/16, 94%) than in females (4/9, 44%) (p=1.2x10(-2)). No siginificant difference was observed in the incidence of the L265P mutation between BSiE1 digestion and allele-specific polymerase chain reaction (p=0.32). These results suggest that the L265P mutation is involved in the majority of Waldenström’s macroglobulinemia. BSiE1 digestion and allele-specific polymerase chain reaction may detect a small fraction of mutated cells in some cases.
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spelling pubmed-38182422013-11-09 L265P Mutation of the MYD88 Gene Is Frequent in Waldenström’s Macroglobulinemia and Its Absence in Myeloma Mori, Naoki Ohwashi, Mari Yoshinaga, Kentaro Mitsuhashi, Kenjiro Tanaka, Norina Teramura, Masanao Okada, Michiko Shiseki, Masayuki Tanaka, Junji Motoji, Toshiko PLoS One Research Article L265P mutation in the MYD88 gene has recently been reported in Waldenström’s macroglobulinemia; however the incidence has been different according to the methods used. To determine the relevance and compare the incidence by different methods, we analyzed the L265P mutation in bone marrow mononuclear cells from lymphoid neoplasms. We first performed cloning and sequencing in 10 patients: 8 Waldenström’s macroglobulinemia; 1 non-IgM-secreting lymphoplasmacytic lymphoma; and 1 low grade B-cell lymphoma with monoclonal IgG protein. The L265P mutation was detected in only 1/8 Waldenström’s macroglobulinemia patients (2 of 9 clones). To confirm these results, direct sequencing was performed in the 10 patients and an additional 17 Waldenström’s macroglobulinemia patients and 1 lymphoplasmacytic lymphoma patient. Nine of 28 patients (7/25 Waldenström’s macroglobulinemia, 1/2 lymphoplasmacytic lymphoma, and B-cell lymphoma) harbored the mutation. We next tested for the mutation with BSiE1 digestion and allele-specific polymerase chain reaction in the 28 patients and 38 patients with myeloma. Aberrant bands corresponding to the mutation were detected by BSiE1 digestion in 19/25 patients with Waldenström’s macroglobulinemia (76%), 1/2 lymphoplasmacytic lymphoma and B-cell lymphoma, but not in the 38 myeloma patients. The L265P mutation was more frequent in patients with Waldenström’s macroglobulinemia than in those with myeloma (p=1.3x10(-10)). The mutation was detected by allele-specific polymerase chain reaction in 18/25 Waldenström’s macroglobulinemia patients (72%). In the 25 Waldenström’s macroglobulinemia patients, the L265P was more frequently detected by BSiE1 digestion than by direct sequencing (p=5.3x10(-4)), and in males (15/16, 94%) than in females (4/9, 44%) (p=1.2x10(-2)). No siginificant difference was observed in the incidence of the L265P mutation between BSiE1 digestion and allele-specific polymerase chain reaction (p=0.32). These results suggest that the L265P mutation is involved in the majority of Waldenström’s macroglobulinemia. BSiE1 digestion and allele-specific polymerase chain reaction may detect a small fraction of mutated cells in some cases. Public Library of Science 2013-11-05 /pmc/articles/PMC3818242/ /pubmed/24224040 http://dx.doi.org/10.1371/journal.pone.0080088 Text en © 2013 Mori et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mori, Naoki
Ohwashi, Mari
Yoshinaga, Kentaro
Mitsuhashi, Kenjiro
Tanaka, Norina
Teramura, Masanao
Okada, Michiko
Shiseki, Masayuki
Tanaka, Junji
Motoji, Toshiko
L265P Mutation of the MYD88 Gene Is Frequent in Waldenström’s Macroglobulinemia and Its Absence in Myeloma
title L265P Mutation of the MYD88 Gene Is Frequent in Waldenström’s Macroglobulinemia and Its Absence in Myeloma
title_full L265P Mutation of the MYD88 Gene Is Frequent in Waldenström’s Macroglobulinemia and Its Absence in Myeloma
title_fullStr L265P Mutation of the MYD88 Gene Is Frequent in Waldenström’s Macroglobulinemia and Its Absence in Myeloma
title_full_unstemmed L265P Mutation of the MYD88 Gene Is Frequent in Waldenström’s Macroglobulinemia and Its Absence in Myeloma
title_short L265P Mutation of the MYD88 Gene Is Frequent in Waldenström’s Macroglobulinemia and Its Absence in Myeloma
title_sort l265p mutation of the myd88 gene is frequent in waldenström’s macroglobulinemia and its absence in myeloma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818242/
https://www.ncbi.nlm.nih.gov/pubmed/24224040
http://dx.doi.org/10.1371/journal.pone.0080088
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