High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis

被引：267

作者：

Brown, Noah A. ^{[1
]}

Furtado, Larissa V. ^{[2
]}

Betz, Bryan L. ^{[1
]}

Kiel, Mark J. ^{[1
]}

Weigelin, Helmut C. ^{[1
]}

Lim, Megan S. ^{[1
]}

Elenitoba-Johnson, Kojo S. J. ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[2] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA

来源：

BLOOD | 2014年 / 124卷 / 10期

关键词：

INHIBITOR SELUMETINIB AZD6244; LUNG ADENOCARCINOMA; MELANOMA; MEK; RESISTANCE; DISEASE;

D O I：

10.1182/blood-2014-05-577361

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Langerhans cell histiocytosis (LCH) represents a clonal proliferation of Langerhans cells. BRAF V600E mutations have been identified in approximately 50% of cases. To discover other genetic mechanisms underlying LCH pathogenesis, we studied 8 cases of LCH using a targeted next-generation sequencing platform. An E102_I103del mutation in MAP2K1 was identified in one BRAF wild-type case and confirmed by Sanger sequencing. Analysis of 32 additional cases using BRAF V600E allele-specific polymerase chain reaction and Sanger sequencing of MAP2K1 exons 2 and 3 revealed somatic, mutually exclusive BRAF and MAP2K1 mutations in 18 of 40 (45.0%) and 11 of 40 (27.5%) cases, respectively. This is the first report of MAP2K1 mutations in LCH that occur in 50% of BRAF wild-type cases. The mutually exclusive nature of MAP2K1 and BRAF mutations implicates a critical role of oncogenic MAPK signaling in LCH. This finding may also have implications in the use of BRAF and MEK inhibitor therapy.

引用

页码：1655 / 1658

页数：4

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