title: Cutaneous basal cell carcinosarcomas: evidence of clonality and recurrent chromosomal losses.
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.
authors.affiliation: 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.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Harms
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor MI 48109.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Fullen
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor MI 48109.
authors.forename: Rajiv M
authors.initials: RM
authors.lastname: Patel
authors.affiliation: Department of Dermatology, University of Michigan Health System, Ann Arbor MI 48109.
authors.forename: Dannie
authors.initials: D
authors.lastname: Chang
authors.affiliation: Departments of Pathology and Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR 72205.
authors.forename: Sara C
authors.initials: SC
authors.lastname: Shalin
authors.affiliation: Miraca Life Sciences, Glen Burnie, MD 21061.
authors.forename: Linglei
authors.initials: L
authors.lastname: Ma
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wood
authors.affiliation: CliniPath Pathology, Osborne Park, WA 6017, Australia.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Beer
authors.affiliation: 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.
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.affiliation: Department of Urology, Henry Ford Health System, Detroit, MI 48202.
authors.forename: Shannon
authors.initials: S
authors.lastname: Carskadon
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor MI 48109.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.affiliation: Department of Dermatology, University of Michigan Health System, Ann Arbor MI 48109.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Fisher
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor MI 48109.
authors.forename: Aleodor
authors.initials: A
authors.lastname: Andea
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002296:Carcinosarcoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D012008:Recurrence; D012878:Skin Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Basal cell carcinoma; Carcinosarcoma; Clonality; Copy number analysis; Osteosarcoma; TP53