title: IDH1 R132C mutation is detected in clear cell hepatocellular carcinoma by pyrosequencing.
abstract: BACKGROUND
  Isocitrate dehydrogenase 1 (IDH1) mutation is common in low-grade glioma (approximately 80%) and acute myeloid leukemia (approximately 10%). Other than brain tumor or hematologic malignancies, intrahepatic cholangiocarcinoma (iCC) is a well-known solid tumor with IDH1 mutation (6.8-20%). Histologically, poor differentiation and clear cell change are associated with IDH1 mutation in iCC. Since hepatocellular carcinoma (HCC) shares histologic features with iCC, some specific subtypes of HCC might show a higher IDH1 mutation rate than reported before (0.5-1.5%).
  
  
  METHODS
  Forty-six cases of iCC and 48 cases of HCC (including 20 cases of clear cell type and 13 cases of pseudoglandular pattern) were tested for IDH1 mutation by pyrosequencing.
  
  
  RESULTS
  Three cases in iCC (6.5%) and five cases in HCC (10.4%) had IDH1 mutation, all of which were Arg132Cys. IDH1 mutant HCCs were all clear cell type. Although the IDH1 mutation rate between iCC and HCC demonstrated no significant difference, clear cell HCC revealed statistically increased mutation rate compared to that of HCC without clear cell change (P = 0.009). Presence of IDH1 mutation was related with poor survival in clear cell HCC patients (P = 0.004).
  
  
  CONCLUSIONS
  Clear cell HCC showed higher frequency of IDH1 mutation rate than other variants of HCC. This result consolidates the assumption that morphological features of tumors reflect molecular alterations.
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.|Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 50612, South Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.|Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 50612, South Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Shin
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.
authors.forename: Won Young
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Shin
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.
authors.forename: Ahrong
authors.initials: A
authors.lastname: Kim
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.
authors.forename: Young Keum
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.
authors.forename: Kyung Un
authors.initials: KU
authors.lastname: Choi
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.
authors.forename: Jee Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan, 47392, South Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yang
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea.
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, 50612, South Korea. mysol@pusan.ac.kr.
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Sol
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D017422:Sequence Analysis, DNA / Q000379:methods*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: Clear cell carcinoma; Hepatocellular carcinoma; IDH; Pyrosequencing