Deep sequencing reveals double mutations in cis of MPL exon 10 in myelloproliferative neoplasm's

作者：Pietra Daniela^*; Brisci Angela; Rumi Elisa; Boggi Sabrina; Elena Chiara; Pietrelli Alessandro; Bordoni Roberta; Ferrari Maurizio; Passamonti Francesco; De Bellis Gianluca; Cremonesi Laura; Cazzola Mario

来源：Haematologica-The Hematology Journal, 2011, 96(4): 607-611.

DOI：10.3324/haematol.2010.034793

• myeloproliferative neoplasm
• MPL exon 10
• deep sequencing
• mutation

Somatic mutations of MPL exon 10, mainly involving a W515 substitution, have been described in JAK2 (V617F)-negative patients with essential thrombocythemia and primary myelofibrosis. We used direct sequencing and nigh-resolution melt analysis to identify mutations of MPL exon 10 in 570 patients with myeloproliferative neoplasms, and allele specific PCR and deep sequencing to further charactelize a subset of mutated patients. Somatic mutations were detected in 33 of 221 patients (15%) with JAK2 (V617F)-negative essential thrombocythemia or primary myelofibrosis. Only one patient with essential thrombocythemia carried both JAK2 (V617F) and MPL (W515L). High-resolution melt analysis identified abnormal patterns in all the MPL mutated cases, while direct sequencing did not detect the mutant MPL in one fifth of them. In 3 cases carrying double MPL mutations, deep sequencing analysis showed identical load and location in cis of the paired lesions, indicating their simultaneous occurrence on the same chromosome.

• 出版日期2011-4