title: MYD88 L265P mutations are correlated with 6q deletion in Korean patients with Waldenström macroglobulinemia.
abstract: Waldenström macroglobulinemia (WM) is a malignant lymphoplasma-proliferative disorder with IgM monoclonal gammopathy. A recent whole-genome study identified MYD88 L265P as the key mutation in WM. We investigated MYD88 mutations in conjunction with cytogenetic study in 22 consecutive Korean WM patients. Conventional G-banding and interphase fluorescence in situ hybridization (FISH) were performed at regions including 6q21 using bone marrow (BM) aspirates. Sixteen patients were subjected to Sanger sequencing-based MYD88 mutation study. Five patients (28%) showed cytogenetic aberrations in G-banding. The incidence of 6q21 deletion was 17% by conventional G-banding and 37% by FISH. Ten patients (45%) showed cytogenetic aberrations using FISH: 6q deletion in eight (37%) and IGH rearrangement in four (18%). Two patients had both the 6q deletion and IGH rearrangement, and two had only the IGH rearrangement. Eleven patients (69%) presented with the MYD88 L265P mutation. MYD88 mutations were significantly associated with the presence of 6q deletions (P = 0.037). Six patients with the 6q deletion for whom sequencing was possible were found to harbor MYD88 mutations. The MYD88 L265P mutation was also associated with increased lymphocyte burden in BM biopsy. This is the first report of high frequency MYD88 L265P mutations in Korean WM patients.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyongok
authors.initials: K
authors.lastname: Im
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Si Nae
authors.identifier: 0000-0002-6455-1528
authors.initials: SN
authors.lastname: Park
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jiseok
authors.initials: J
authors.lastname: Kwon
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Qute
authors.initials: Q
authors.lastname: Choi
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea ; Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Sang Mee
authors.identifier: 0000-0003-3390-1932
authors.initials: SM
authors.lastname: Hwang
authors.affiliation: Hematology Division, National Hospital Organization Disaster Medical Center, Tokyo, Japan.
authors.forename: Naohiro
authors.identifier: 0000-0001-9860-8257
authors.initials: N
authors.lastname: Sekiguchi
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Seon Young
authors.identifier: 0000-0001-5459-9635
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D018570:Risk Assessment; D013223:Statistics as Topic; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88