کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5660721 1407496 2017 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Exome analysis of the evolutionary path of hepatocellular adenoma-carcinoma transition, vascular invasion and brain dissemination
ترجمه فارسی عنوان
تجزیه و تحلیل عاملی از مسیر تکاملی انتقال آدرنوم-کارسینوم هپاتوسلولار، تهاجم عروقی و انتشار مغزی
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
چکیده انگلیسی

SummaryHepatocellular adenoma (HCA) is a rare benign liver tumor, predominantly seen in young women. Its major complications are malignant transformation, spontaneous hemorrhage, and rupture. We describe a case of a young female with no underlying liver disease who presented with acute abdominal pain and was found to have a 17 cm heterogeneous mass in the left lobe of the liver. She underwent left hepatectomy and pathology revealed a 14 cm moderately differentiated hepatocellular carcinoma (HCC) arising in a shell of a HCA. At that time, vascular invasion was already present. She rapidly developed recurrent multifocal hepatic lesions and subsequent spread to the brain, leading to her death 18 months after surgery. To investigate the underlying genetic events occurring during hepatocellular adenoma-carcinoma transition and extra-hepatic dissemination, we performed whole exome sequencing of DNA isolated from peripheral blood leucocytes, HCA, HCC, tumor thrombus and brain metastasis. Our data show a step-wise addition of somatic mutations and copy number variations with disease progression, suggesting a linear tumor evolution, which is supported by clonality analysis. Specifically, using a model based clustering of somatic mutations, one single founding clone arising in the HCA, which included catenin beta 1 (CTNNB1) and IL6ST driver mutations, was identified and displayed an increasing clonality rate in HCC, tumor thrombus and brain metastasis. Our data highlight the feasibility of performing whole exome capture, sequencing and analysis using formalin-fixed paraffin-embedded (FFPE) samples, and we describe the first genomic longitudinal study of hepatocellular adenoma-carcinoma transition, vascular invasion and brain metastasis with detailed clinicopathologic annotation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 67, Issue 1, July 2017, Pages 186-191
نویسندگان
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