PMID- 36370823
OWN - NLM
STAT- MEDLINE
DCOM- 20230112
LR  - 20240412
IS  - 1532-8392 (Electronic)
IS  - 0046-8177 (Print)
IS  - 0046-8177 (Linking)
VI  - 131
DP  - 2023 Jan
TI  - Alternative lengthening of telomeres in primary hepatic neoplasms.
PG  - 79-86
LID - S0046-8177(22)00260-X [pii]
LID - 10.1016/j.humpath.2022.11.003 [doi]
AB  - The alternative lengthening of telomeres (ALT) phenotype is characterized by 
      ultra-bright telomeres on fluorescence in situ hybridization (FISH) and is a 
      marker of a unique mechanism of telomere maintenance in tumors. ALT does not 
      occur in normal tissues. ALT has been described in hepatocellular carcinoma 
      (5-10%) and in primary hepatic angiosarcomas (75%). To study the frequency of ALT 
      in other primary hepatic tumors, a wide range of primary hepatic neoplasms were 
      retrieved. The tumors included the following: intrahepatic and hilar 
      cholangiocarcinomas (N = 110), hepatic adenomas (N = 35), hepatocellular 
      carcinomas (N = 30), fibrolamellar carcinomas (n = 11), combined 
      cholangiocarcinoma-hepatocellular carcinomas (N = 8), carcinosarcoma (N = 10), 
      hepatoblastomas (N = 5), hemangiomas (N = 4), angiosarcomas (N = 8), epithelioid 
      hemangioendotheliomas (N = 10), calcified nested stromal epithelial tumor 
      (N = 2), embryonal sarcoma (N = 2), rhabdoid tumor (N = 1), bile duct adenoma 
      (N = 1), and angiomyolipoma (N = 1). For epithelial tumors, ALT-FISH was positive 
      in one carcinosarcoma (10% of cases), one cholangiocarcinoma (1% of cases), and 
      one combined hepatocellular carcinoma-cholangiocarcinoma (13% of cases). In the 
      hepatocellular carcinoma component of both the carcinosarcoma and the combined 
      hepatocellular carcinoma-cholangiocarcinoma, the tumor cells showed patchy marked 
      nuclear pleomorphism akin to that described previously for chromophobe 
      hepatocellular carcinoma, which are typically ALT FISH positive. The ALT-positive 
      cholangiocarcinoma also showed patchy, striking nuclear pleomorphism. For soft 
      tissue tumors, ALT was positive in two angiosarcomas (N = 2; 25% of cases). In 
      summary, this study shows that ALT-FISH is positive in rare carcinosarcomas, 
      cholangiocarcinomas, and combined cholangiocarcinoma-hepatocellular carcinoma. 
      ALT is not a significant mechanism of telomere maintenance in hepatocellular 
      adenomas or fibrolamellar carcinomas and was negative in all other tested primary 
      hepatic neoplasms. ALT-FISH is also positive in a subset of primary hepatic 
      angiosarcomas.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Yasir, Saba
AU  - Yasir S
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 
      55905, USA.
FAU - Thompson, Scott
AU  - Thompson S
AD  - Department of Radiology, Mayo Clinic Rochester, MN, 55905, USA.
FAU - Chen, Zongming Eric
AU  - Chen ZE
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 
      55905, USA.
FAU - Knudson, Ryan
AU  - Knudson R
AD  - Medical Genome Facility, Cytogenetics Core Laboratory, Mayo Clinic Rochester, MN, 
      55905, USA.
FAU - Knutson, Darlene
AU  - Knutson D
AD  - Medical Genome Facility, Cytogenetics Core Laboratory, Mayo Clinic Rochester, MN, 
      55905, USA.
FAU - Kloft-Nelson, Sara
AU  - Kloft-Nelson S
AD  - Medical Genome Facility, Cytogenetics Core Laboratory, Mayo Clinic Rochester, MN, 
      55905, USA.
FAU - Graham, Rondell P
AU  - Graham RP
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 
      55905, USA.
FAU - Jain, Dhanpat
AU  - Jain D
AD  - Department Pathology, Yale, CT, 06520, USA.
FAU - Simon, Sanford M
AU  - Simon SM
AD  - Laboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, 
      NY, NY, 10065, USA.
FAU - Wu, Tsung-Teh
AU  - Wu TT
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 
      55905, USA.
FAU - Torbenson, Michael
AU  - Torbenson M
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 
      55905, USA. Electronic address: Torbenson.Michael@mayo.edu.
LA  - eng
GR  - P50 CA210964/CA/NCI NIH HHS/United States
GR  - U54 CA243126/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20221109
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - Fibrolamellar hepatocellular carcinoma
SB  - IM
MH  - Humans
MH  - *Carcinoma, Hepatocellular/genetics/pathology
MH  - *Hemangiosarcoma/genetics/pathology
MH  - In Situ Hybridization, Fluorescence
MH  - *Liver Neoplasms/genetics/pathology
MH  - *Cholangiocarcinoma/genetics/pathology
MH  - *Carcinosarcoma/pathology
MH  - Bile Ducts, Intrahepatic/pathology
MH  - *Bile Duct Neoplasms/genetics/pathology
MH  - Telomere/genetics/pathology
PMC - PMC10756352
MID - NIHMS1849261
OTO - NOTNLM
OT  - Alternative lenthening of telomeres
OT  - Angiosarcoma
OT  - Carcinosarcoma
OT  - Cholangiocarcinoma
OT  - Combined hepatocellular carcinoma-cholangiocarcinoma
OT  - Fibrolamellar carcinoma
OT  - Hepatocellular carcinoma
COIS- Conflicts of interest: The authors declare no conflict of interest
EDAT- 2022/11/13 06:00
MHDA- 2023/01/13 06:00
PMCR- 2024/01/01
CRDT- 2022/11/12 19:33
PHST- 2022/08/16 00:00 [received]
PHST- 2022/10/31 00:00 [revised]
PHST- 2022/11/04 00:00 [accepted]
PHST- 2022/11/13 06:00 [pubmed]
PHST- 2023/01/13 06:00 [medline]
PHST- 2022/11/12 19:33 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - S0046-8177(22)00260-X [pii]
AID - 10.1016/j.humpath.2022.11.003 [doi]
PST - ppublish
SO  - Hum Pathol. 2023 Jan;131:79-86. doi: 10.1016/j.humpath.2022.11.003. Epub 2022 Nov 
      9.