DICER1 mutations in twelve Chinese patients with pleuropulmonary blastoma

Abstract

Our aim is to examine the impact of DICER1 mutations on the pathogenesis of pleuropulmonary blastoma (PPB) by evaluating the mutation frequency and investigating the family history of Chinese patients with PPB. The family histories of 12 children with PPB recruited consecutively were surveyed. Blood samples from patients and their first-degree relatives were tested for DICER1 mutations. Whole-genome sequencing of blood samples and formalin-fixed and paraffin-embedded (FFPE) tumor tissue was performed in one family with twins. Twelve patients with PPB included six type II and six type III cases. Seven of the 12 patients harbored DICER1 mutations, six of which were frameshift or nonsense mutations. Another case carried a germline DICER1 mutation affecting the splice site. FFPE sample had a nonsense mutation in TDG and missense mutations in DICER1. In addition, two cases with DICER1 mutations were found to have lung cysts preceding the diagnosis of PPB. Furthermore, one patient had a family history remarkable for thyroid diseases. Our results indicate that the germline mutation frequency in Chinese patients with PPB is similar to the ones reported for patients from USA, UK, and Japan. Moreover, our study strongly suggests that investigating the family history and detecting germline DICER1 mutations might be of benefit to increasing awareness and improving the accuracy of the differential diagnosis of PPB from non-malignant lung cysts.

Clinical and molecular features of pleuropulmonary blastoma in children in Hong Kong: case reports

“…In our series, novel heterozygous germline DICER1 frameshift mutations were found in cases 2 and 3; while a heterozygous germline nonsense mutation, reported recently in another Chinese patient, was detected in Case 4 (Fig 4). 4 The findings of our case series add to the spectrum of known DICER1 mutations, especially to the very limited data from Asia. 4 Diagnosing DICER1 syndrome facilitates surveillance of associated morbidities, familial testing and reproductive counselling for both probands and symptomatic carriers.…”

“…4 The findings of our case series add to the spectrum of known DICER1 mutations, especially to the very limited data from Asia. 4 Diagnosing DICER1 syndrome facilitates surveillance of associated morbidities, familial testing and reproductive counselling for both probands and symptomatic carriers. 5 Further studies and consideration of a prospective patient registry to define the prevalence of DICER1-associated conditions in both paediatric and adult populations in Hong Kong are warranted.…”

Outcome of two pairs of monozygotic twins with pleuropulmonary blastoma: case report

“…As our previous study reported, wholegenome sequencing of blood samples identified 6,361, 526 germline variants in this family (her mother and her sister), including the mutation identified by targeted sequencing (c.C3675A). In addition, the tumour tissue of Twin1 and Twin2 harboured a nonsynonymous variant of DICER1 (c.G5125A) [15]. However, no DICER1 mutations were found in Case 2 in the peripheral blood samples of either twin or their mother.…”

Clinical analysis of early death in children with pleuropulmonary blastoma in a single center in China

“…Many PPBs may initially manifest as pulmonary multilocular cysts with subsequent progression . This malignancy is highly aggressive, and types II and III grow rapidly. The pathology of PPB is a dynamic continuum.…”