PMID- 34476330
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20220323
IS  - 2473-4284 (Electronic)
IS  - 2473-4284 (Linking)
VI  - 5
DP  - 2021 Aug
TI  - Genomic Profiling of Combined Hepatocellular Cholangiocarcinoma Reveals Genomics 
      Similar to Either Hepatocellular Carcinoma or Cholangiocarcinoma.
LID - PO.20.00397 [pii]
LID - 10.1200/PO.20.00397 [doi]
AB  - PURPOSE: Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare, 
      aggressive primary liver carcinoma, with morphologic features of both 
      hepatocellular carcinomas (HCC) and liver cholangiocarcinomas (CCA). METHODS: The 
      genomic profiles of 4,975 CCA, 1,470 HCC, and 73 cHCC-CCA cases arising from 
      comprehensive genomic profiling in the course of clinical care were reviewed for 
      genomic alterations (GA), tumor mutational burden, microsatellite instability 
      status, genomic loss of heterozygosity, chromosomal aneuploidy, genomic ancestry, 
      and hepatitis B virus status. RESULTS: In cHCC-CCA, GA were most common in TP53 
      (65.8%), TERT (49.3%), and PTEN (9.6%), and 24.6% cHCC-CCA harbored potentially 
      targetable GA. Other GA were predominantly associated with either HCC or CCA, 
      including, but not limited to, TERT, FGFR2, IDH1, and presence of hepatitis B 
      virus. On the basis of these features, a machine learning (ML) model was trained 
      to classify a cHCC-CCA case as CCA-like or HCC-like. Of cHCC-CCA cases, 16% 
      (12/73) were ML-classified as CCA-like and 58% (42/73) cHCC-CCA were 
      ML-classified as HCC-like. The ML model classified more than 70% of cHCC-CCA as 
      CCA-like or HCC-like on the basis of genomic profiles, without additional 
      clinico-pathologic input. CONCLUSION: These findings demonstrate the use of ML 
      for classification as based on a targeted exome panel used during routine 
      clinical care. Classification of cHCC-CCA by genomic features alone creates 
      insights into the biology of the disease and warrants further investigation for 
      relevance to clinical care.
CI  - (c) 2021 by American Society of Clinical Oncology.
FAU - Murugesan, Karthikeyan
AU  - Murugesan K
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Sharaf, Radwa
AU  - Sharaf R
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Montesion, Meagan
AU  - Montesion M
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Moore, Jay A
AU  - Moore JA
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Pao, James
AU  - Pao J
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Pavlick, Dean C
AU  - Pavlick DC
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Frampton, Garrett M
AU  - Frampton GM
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Upadhyay, Vivek A
AU  - Upadhyay VA
AD  - Foundation Medicine Inc, Cambridge, MA.
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA.
FAU - Alexander, Brian M
AU  - Alexander BM
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Miller, Vincent A
AU  - Miller VA
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Javle, Milind M
AU  - Javle MM
AD  - Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson 
      Cancer Center, Houston, TX.
FAU - Bekaii Saab, Tanios S
AU  - Bekaii Saab TS
AD  - Mayo Clinic Cancer Center, Phoenix, AZ.
FAU - Albacker, Lee A
AU  - Albacker LA
AD  - Foundation Medicine Inc, Cambridge, MA.
FAU - Ross, Jeffrey S
AU  - Ross JS
AD  - Foundation Medicine Inc, Cambridge, MA.
AD  - Department of Pathology, State University of New York Upstate Medical University, 
      Syracuse, NY.
FAU - Ali, Siraj M
AU  - Ali SM
AD  - Foundation Medicine Inc, Cambridge, MA.
LA  - eng
PT  - Journal Article
DEP - 20210819
PL  - United States
TA  - JCO Precis Oncol
JT  - JCO precision oncology
JID - 101705370
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Bile Duct Neoplasms/*genetics/pathology
MH  - Carcinoma, Hepatocellular/*genetics/pathology
MH  - Cholangiocarcinoma/*genetics/pathology
MH  - Female
MH  - Genomics
MH  - Humans
MH  - Liver/pathology
MH  - Liver Neoplasms/*genetics/pathology
MH  - Machine Learning
MH  - Male
MH  - Middle Aged
MH  - Young Adult
PMC - PMC8384404
COIS- Karthikeyan Murugesan Employment: Foundation Medicine Stock and Other Ownership 
      Interests: Roche Pharma AG Patents, Royalties, Other Intellectual Property: 
      Antibiotic resistance causation identification (US10629291B2) filed with 
      Koninklijke Philips NV, Analytic prediction of antibiotic susceptibility 
      (US20190279738A1) filed with Koninklijke Philips NV, Methods and devices for 
      characterizing and treating combined hepatocellular cholangiocarcinoma, with 
      Foundation Medicine Inc Travel, Accommodations, Expenses: Foundation Medicine 
      Radwa Sharaf Employment: Foundation Medicine Stock and Other Ownership Interests: 
      Roche Meagan Montesion Employment: Foundation Medicine Stock and Other Ownership 
      Interests: Roche Jay A. Moore Employment: Foundation Medicine Stock and Other 
      Ownership Interests: Roche James Pao Employment: Foundation Medicine Stock and 
      Other Ownership Interests: Roche Research Funding: Foundation Medicine Patents, 
      Royalties, Other Intellectual Property: Provisional patent submitted for 
      Foundation Medicine, dealing with machine learning for gene predictions Dean C. 
      Pavlick Employment: Foundation Medicine Stock and Other Ownership Interests: 
      Roche Garrett M. Frampton Employment: Foundation Medicine Stock and Other 
      Ownership Interests: Roche Vivek A. Upadhyay Employment: EQRx Stock and Other 
      Ownership Interests: EQRx Consulting or Advisory Role: Foundation Medicine Brian 
      M. Alexander Employment: Foundation Medicine Leadership: Foundation Medicine 
      Stock and Other Ownership Interests: Roche Research Funding: Lilly, Puma 
      Biotechnology, Celgene Open Payments Link: 
      https://openpaymentsdata.cms.gov/physician/854258/summary Vincent A. Miller 
      Employment: Foundation Medicine, EQRx Leadership: Revolution Medicines Stock and 
      Other Ownership Interests: Foundation Medicine, Mirati Therapeutics, Revolution 
      Medicines, EQRx Patents, Royalties, Other Intellectual Property: Receives 
      periodic royalties related to T790M patent awarded to Memorial Sloan Kettering 
      Cancer Center Milind M. Javle Consulting or Advisory Role: QED Therapeutics, 
      Oncosil, Incyte, Mundipharma EDO GmbH, AstraZeneca, Merck, EMD Serono Other 
      Relationship: Rafael Pharmaceuticals, Incyte, Pieris Pharmaceuticals, Merck, 
      Merck Serono, Novartis, Seattle Genetics, BeiGene, QED Therapeutics, Bayer Tanios 
      S. Bekaii Saab Consulting or Advisory Role: Amgen, Ipsen, Lilly, Bayer, 
      Roche/Genentech, AbbVie, Incyte, Immuneering, Seattle Genetics, Pfizer, 
      Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, 
      Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation Medicine 
      Patents, Royalties, Other Intellectual Property: Patent WO/2018/183488, Patent 
      WO/2019/055687 Other Relationship: Exelixis, Merck, AstraZeneca, Lilly, 
      Pancreatic Cancer Action Network Lee A. Albacker Employment: Foundation Medicine 
      Stock and Other Ownership Interests: Roche Jeffrey S. Ross Employment: Foundation 
      Medicine Leadership: Foundation Medicine Stock and Other Ownership Interests: 
      Foundation Medicine Consulting or Advisory Role: Celsius Therapeutics, Tango 
      Therapeutics Research Funding: Foundation Medicine Siraj M. Ali Employment: EQRx 
      Consulting or Advisory Role: Elevation Oncology, In8bio, Pillar Biosciences, 
      Takeda, ArcherDx Stock and Other Ownership Interests: In8bio, Pillar Biosciences, 
      EQRx Patents: Foundation Medicine No other potential conflicts of interest were 
      reported. Karthikeyan Murugesan Employment: Foundation Medicine Stock and Other 
      Ownership Interests: Roche Pharma AG Patents, Royalties, Other Intellectual 
      Property: Antibiotic resistance causation identification (US10629291B2) filed 
      with Koninklijke Philips NV, Analytic prediction of antibiotic susceptibility 
      (US20190279738A1) filed with Koninklijke Philips NV, Methods and devices for 
      characterizing and treating combined hepatocellular cholangiocarcinoma, with 
      Foundation Medicine Inc Travel, Accommodations, Expenses: Foundation Medicine 
      Radwa Sharaf Employment: Foundation Medicine Stock and Other Ownership Interests: 
      Roche Meagan Montesion Employment: Foundation Medicine Stock and Other Ownership 
      Interests: Roche Jay A. Moore Employment: Foundation Medicine Stock and Other 
      Ownership Interests: Roche James Pao Employment: Foundation Medicine Stock and 
      Other Ownership Interests: Roche Research Funding: Foundation Medicine Patents, 
      Royalties, Other Intellectual Property: Provisional patent submitted for 
      Foundation Medicine, dealing with machine learning for gene predictions Dean C. 
      Pavlick Employment: Foundation Medicine Stock and Other Ownership Interests: 
      Roche Garrett M. Frampton Employment: Foundation Medicine Stock and Other 
      Ownership Interests: Roche Vivek A. Upadhyay Employment: EQRx Stock and Other 
      Ownership Interests: EQRx Consulting or Advisory Role: Foundation Medicine Brian 
      M. Alexander Employment: Foundation Medicine Leadership: Foundation Medicine 
      Stock and Other Ownership Interests: Roche Research Funding: Lilly, Puma 
      Biotechnology, Celgene Open Payments Link: 
      https://openpaymentsdata.cms.gov/physician/854258/summary Vincent A. Miller 
      Employment: Foundation Medicine, EQRx Leadership: Revolution Medicines Stock and 
      Other Ownership Interests: Foundation Medicine, Mirati Therapeutics, Revolution 
      Medicines, EQRx Patents, Royalties, Other Intellectual Property: Receives 
      periodic royalties related to T790M patent awarded to Memorial Sloan Kettering 
      Cancer Center Milind M. Javle Consulting or Advisory Role: QED Therapeutics, 
      Oncosil, Incyte, Mundipharma EDO GmbH, AstraZeneca, Merck, EMD Serono Other 
      Relationship: Rafael Pharmaceuticals, Incyte, Pieris Pharmaceuticals, Merck, 
      Merck Serono, Novartis, Seattle Genetics, BeiGene, QED Therapeutics, Bayer Tanios 
      S. Bekaii Saab Consulting or Advisory Role: Amgen, Ipsen, Lilly, Bayer, 
      Roche/Genentech, AbbVie, Incyte, Immuneering, Seattle Genetics, Pfizer, 
      Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, 
      Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation Medicine 
      Patents, Royalties, Other Intellectual Property: Patent WO/2018/183488, Patent 
      WO/2019/055687 Other Relationship: Exelixis, Merck, AstraZeneca, Lilly, 
      Pancreatic Cancer Action Network Lee A. Albacker Employment: Foundation Medicine 
      Stock and Other Ownership Interests: Roche Jeffrey S. Ross Employment: Foundation 
      Medicine Leadership: Foundation Medicine Stock and Other Ownership Interests: 
      Foundation Medicine Consulting or Advisory Role: Celsius Therapeutics, Tango 
      Therapeutics Research Funding: Foundation Medicine Siraj M. Ali Employment: EQRx 
      Consulting or Advisory Role: Elevation Oncology, In8bio, Pillar Biosciences, 
      Takeda, ArcherDx Stock and Other Ownership Interests: In8bio, Pillar Biosciences, 
      EQRx Patents: Foundation Medicine No other potential conflicts of interest were 
      reported.
EDAT- 2021/09/04 06:00
MHDA- 2021/09/04 06:01
PMCR- 2021/08/19
CRDT- 2021/09/03 06:54
PHST- 2020/10/05 00:00 [received]
PHST- 2021/03/05 00:00 [revised]
PHST- 2021/06/11 00:00 [accepted]
PHST- 2021/09/03 06:54 [entrez]
PHST- 2021/09/04 06:00 [pubmed]
PHST- 2021/09/04 06:01 [medline]
PHST- 2021/08/19 00:00 [pmc-release]
AID - PO.20.00397 [pii]
AID - 10.1200/PO.20.00397 [doi]
PST - epublish
SO  - JCO Precis Oncol. 2021 Aug 19;5:PO.20.00397. doi: 10.1200/PO.20.00397. 
      eCollection 2021 Aug.