Format

Send to

Choose Destination
Hum Pathol. 2015 May;46(5):690-7. doi: 10.1016/j.humpath.2015.01.006. Epub 2015 Jan 14.

Cutaneous basal cell carcinosarcomas: evidence of clonality and recurrent chromosomal losses.

Author information

1
Department of Pathology, University of Michigan Health System, Ann Arbor MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor MI 48109; Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor MI 48109. Electronic address: harmsa2fam@gmail.com.
2
Department of Pathology, University of Michigan Health System, Ann Arbor MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor MI 48109.
3
Department of Dermatology, University of Michigan Health System, Ann Arbor MI 48109.
4
Departments of Pathology and Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR 72205.
5
Miraca Life Sciences, Glen Burnie, MD 21061.
6
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
7
CliniPath Pathology, Osborne Park, WA 6017, Australia.
8
Department of Pathology, University of Michigan Health System, Ann Arbor MI 48109; Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor MI 48109.
9
Department of Urology, Henry Ford Health System, Detroit, MI 48202.
10
Department of Pathology, University of Michigan Health System, Ann Arbor MI 48109.
11
Department of Pathology, University of Michigan Health System, Ann Arbor MI 48109; Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor MI 48109; Department of Urology, Henry Ford Health System, Detroit, MI 48202; King Saud University, Riyadh, Saudi Arabia 11362.

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.

KEYWORDS:

Basal cell carcinoma; Carcinosarcoma; Clonality; Copy number analysis; Osteosarcoma; TP53

PMID:
25704628
DOI:
10.1016/j.humpath.2015.01.006
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center