Association of Li-Fraumeni Syndrome With Small Cell Carcinoma of the Ovary, Hypercalcemic Type and Concurrent Pleomorphic Liposarcoma of the Cervix.
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare, highly lethal malignancy predominantly affecting young adult females. We report a patient with widely metastatic SCCOHT and concurrent uterine cervical pleomorphic liposarcoma. Clinical targeted next-generation sequencing was performed on both neoplasms and demonstrated hemizygous stop-gain TP53 mutations (p.R196*), and wild-type SMARCA4 in both tumors. Microarray analyses of both tumors revealed similar but not identical widespread loss of heterozygosity over most chromosomes associated with loss of chromosomal copy number in the SCCOHT and pleomorphic liposarcoma tumors, amplification of FGFR1 in both tumors, and amplification of MYC in the SCCOHT. Immunohistochemistry demonstrated that SMARCA4 and SMARCB1 were retained in both tumors, and that SMARCA2 expression was retained but TP53 expression was lost in the SCCOHT. Germline testing using Sanger sequencing showed heterozygous TP53 mutation, confirming the diagnosis of Li-Fraumeni syndrome. These findings are novel and for the first time associate SCCOHT with Li-Fraumeni syndrome.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO.
Bevan
B
Tandon
Ian S
IS
Hagemann
Horacio M
HM
Maluf
John D
JD
Pfeifer
Hussam
H
Al-Kateb
D018288:Carcinoma, Small Cell / Q000150:complications / Q000235:genetics* / Q000473:pathology; D004265:DNA Helicases / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D006934:Hypercalcemia; D016864:Li-Fraumeni Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008080:Liposarcoma / Q000150:complications / Q000473:pathology*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010053:Ovary / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D000071796:SMARCB1 Protein / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
C489427:MYC protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; C084011:SMARCA2 protein, human; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C084108:SMARCA4 protein, human; D004265:DNA Helicases