Hum Pathol. 2015 Jan 14. pii: S0046-8177(15)00014-3. doi: 10.1016/j.humpath.2015.01.006. [Epub ahead of print]
Cutaneous basal cell carcinosarcomas: evidence of clonality and recurrent chromosomal losses.
Harms PW, Fullen DR, Patel RM, Chang D, Shalin SC, Ma L, Wood B, Beer TW, Siddiqui J, Carskadon S, Wang M, Palanisamy N, Fisher GJ, Andea A.
Abstract
Cutaneous
carcinosarcomas are heterogeneous group of tumors composed of malignant
epithelial and mesenchymal components. Although mutation analyses have
identified clonal changes between these morphologically disparate
components in some subtypes of cutaneous carcinosarcoma, few cases have
been analyzed thus far. To our knowledge, copy number variations (CNVs)
and copy-neutral loss of heterozygosity (CN-LOH) have not been
investigated in cutaneous carcinosarcomas. We analyzed 4 carcinosarcomas
with basal cell carcinoma and osteosarcomatous components for
CNVs/CN-LOH by comparative genomic hybridization/single-nucleotide
polymorphism array, TP53 hot spot mutations by polymerase chain reaction
and Sanger sequencing, and TP53 genomic rearrangements by fluorescence
in situ hybridization. All tumors displayed multiple CNV/CN-LOH events
(median, 7.5 per tumor). Three of 4 tumors displayed similar CNV/CN-LOH
patterns between the epithelial and mesenchymal components within each
tumor, supporting a common clonal origin. Recurrent changes included
allelic loss at 9p21 (CDKN2A), 9q (PTCH1), and 17p (TP53). Allelic
losses of chromosome 16 including CDH1 (E-cadherin) were present in 2
tumors and were restricted to the sarcomatous component. TP53 mutation
analysis revealed an R248L mutation in both epithelial and mesenchymal
components of 1 tumor. No TP53 rearrangements were identified. Our
findings indicate that basal cell carcinosarcomas harbor CNV/CN-LOH
changes similar to conventional basal cell carcinoma, with additional
changes including recurrent 9p21 losses and a relatively high burden of
copy number changes. In addition, most cutaneous carcinosarcomas show
evidence of clonality between epithelial and mesenchymal components.
Published by Elsevier Inc.
Published by Elsevier Inc.
KEYWORDS:Basal cell carcinoma; Carcinosarcoma; Clonality; Copy number analysis; Osteosarcoma; TP53
- PMID:25704628
