RESUMO
Angiomyolipoma (AML) is classified as a perivascular epithelioid cell neoplasm, mostly occurring in the kidney. Twenty percent of patients with renal AML have tuberous sclerosis complex (TSC) caused by germline variation in the TSC1 or TSC2 gene. In this paper, we report the first case of renal AML harboring somatic missense mutations of the TSC2 gene and concomitant copy-neutral loss of heterozygosity (CN-LOH). The patient presented with solitary renal AML and pulmonary lymphangiomyomatosis and without other findings suggestive of TSC. Exome sequencing analysis of the renal AML, however, identified a pathogenic somatic missense mutation in the TSC2 gene (NM_000548:c.5228G>A:p. R1743Q), although no other somatic mutation was detected. Furthermore, no germline mutation in TSC1 or TSC2 was detected. Interestingly, the mutant allele ratio was too high for a somatic heterozygous mutation without loss of heterozygosity (LOH). Furthermore, no copy number variation was detected around the TSC2 locus (16p13.3). To clarify the allelic status, we analyzed heterozygous single-nucleotide polymorphisms (SNPs) in chromosome 16. In these SNPs, an unbalanced allele ratio was accumulated inside the 16p13.3 region. These results suggested copy-neutral LOH (CN-LOH). Consequently, we concluded that the missense mutation of the TSC2 gene and CN-LOH of the TSC2 locus caused renal AML.
Assuntos
Angiomiolipoma/genética , Angiomiolipoma/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Perda de Heterozigosidade , Mutação de Sentido Incorreto , Proteína 2 do Complexo Esclerose Tuberosa/genética , Idoso , Variações do Número de Cópias de DNA , Feminino , Humanos , PrognósticoRESUMO
The patient was a 68-year-old woman who visited a nearby clinic with a chief complaint of right hypochondrial pain. A mass lesion in the gallbladder was found by ultrasonography. She was referred to our hospital for further examination and was diagnosed with gallbladder cancer. Cholecystectomy and bile duct resection were performed. Six months after the surgery, multiple liver metastases were found. A subcutaneous implant reservoir was placed in the hepatic artery from the right femoral artery. After arterial infusion chemotherapy by 5-FU and CDDP, or 5-FU alone, liver metastasis markedly responded and became undetectable, and therapy was therefore discontinued. The patient has been disease-free without any sign of recurrence for 7 months after CR was achieved. It is suggested that arterial infusion chemotherapy is useful and safe for the treatment of liver metastasis from gallbladder cancer.
