Anaplastic
sarcoma of the kidney is a rare
tumor (≤25 reported cases) characterized by the presence of
cysts, and solid areas composed of bundles of undifferentiated spindle cells, showing marked cellular
anaplasia (usually accompanied by TP53 overexpression). These
tumors often feature prominent areas of cartilage or chondroid material. Germline mutations in DICER1, encoding the
microRNA (
miRNA) processor DICER1, cause an eponymous syndrome. Recent reports suggest that anaplastic
sarcoma of the kidney should be included in DICER1 syndrome as germline DICER1 mutations are associated with the occurrence of such
tumors. Therefore, we sought to determine the following: (1) what proportion of anaplastic
sarcoma of the kidney have DICER1 mutations; (2) whether the identified mutations affect both alleles of DICER1 (ie, are biallelic); (3) whether somatic missense mutations in the DICER1
RNase IIIb domain impact
miRNA generation; and (4) whether TP53 alteration always occurs in these
tumors. DICER1 mutations were evaluated by Sanger sequencing and next-generation sequencing in nine
tumor/normal pairs. Impact of DICER1 mutations on
miRNA generation was evaluated via an in vitro DICER1 cleavage assay. TP53 status was assessed by immunohistochemistry and next-generation sequencing. Eight of the nine cases had at least one
RNase IIIb DICER1 mutation that impacted the generation of
miRNAs. There were six
tumors with truncating DICER1 mutations and in four of them, the mutation found in the
tumor was also detected in adjacent normal tissue, and therefore was likely to be either mosaic or germline in origin. Analysis of mutation phase revealed that two of three
tumors had biallelic DICER1 mutations. Six of nine anaplastic
sarcomas of the kidney had aberrant TP53 immunohistochemisty with damaging TP53 mutations identified in three cases. Taken together, these data suggest that the great majority of anaplastic
sarcomas of the kidney have DICER1 mutations and confirm that these
tumors are part of the DICER1 syndrome.