PMID- 34445161
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20240322
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 16
DP  - 2021 Aug 6
TI  - NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC 
      Amplification in Ocular Adnexal Sebaceous Carcinomas.
LID - 10.3390/ijms22168454 [doi]
LID - 8454
AB  - Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive 
      clinical and histopathological phenotypes than extraocular cases, but the 
      molecular drivers implicated in their oncogenesis remain poorly defined. A 
      retrospective review of surgical and ocular pathology archives identified eleven 
      primary resection specimens of OA sebaceous carcinomas with adequate tissue for 
      molecular analysis; two extraocular cases were also examined. Next-generation 
      sequencing was used to evaluate mutations and copy number changes in a large 
      panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) 
      confirmed MYC copy number gain in select cases, and immunohistochemistry to 
      evaluate MYC protein expression. The commonest mutations occurred in TP53 (10/13) 
      and RB1 (7/13). Additional mutations in clinically actionable genes, or mutations 
      with a frequency of at least 25%, included the NF1 (3/12), PMS2 (4/12), ROS1 
      (3/12), KMT2C (4/12), MNX1 (6/12), NOTCH1 (4/12), PCLO (3/12), and PTPRT (3/12) 
      loci. Low level copy number gain suggestive of amplification of the MYC locus was 
      seen in two cases, and confirmed using FISH. MYC protein expression, as assessed 
      by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our 
      findings support the concept that alterations in TP53 and RB1 are the commonest 
      alterations in sebaceous carcinoma, and suggest that MYC may contribute to the 
      oncogenesis of these tumors.
FAU - Peterson, Cornelia
AU  - Peterson C
AUID- ORCID: 0000-0001-6550-1883
AD  - Department of Molecular and Comparative Pathobiology, The Johns Hopkins 
      University School of Medicine, Baltimore, MD 21205, USA.
FAU - Moore, Robert
AU  - Moore R
AD  - Department of Pathology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
FAU - Hicks, Jessica L
AU  - Hicks JL
AD  - Department of Pathology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
FAU - Morsberger, Laura A
AU  - Morsberger LA
AD  - Department of Pathology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
AD  - Clinical Cytogenetics Laboratory, The Johns Hopkins University School of 
      Medicine, Baltimore, MD 21205, USA.
AD  - Johns Hopkins Genomics, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
FAU - De Marzo, Angelo M
AU  - De Marzo AM
AD  - Department of Pathology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
AD  - Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of 
      Medicine, Baltimore, MD 21205, USA.
AD  - The Brady Urological Research Institute, The Johns Hopkins University School of 
      Medicine, Baltimore, MD 21205, USA.
FAU - Zou, Ying
AU  - Zou Y
AD  - Department of Pathology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
AD  - Clinical Cytogenetics Laboratory, The Johns Hopkins University School of 
      Medicine, Baltimore, MD 21205, USA.
AD  - Johns Hopkins Genomics, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
FAU - Eberhart, Charles G
AU  - Eberhart CG
AD  - Department of Pathology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
AD  - Department of Ophthalmology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
FAU - Campbell, Ashley A
AU  - Campbell AA
AD  - Department of Ophthalmology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21205, USA.
LA  - eng
GR  - T32 OD011089/OD/NIH HHS/United States
PT  - Journal Article
DEP - 20210806
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (MYC protein, human)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RB1 protein, human)
RN  - 0 (Retinoblastoma Binding Proteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Eye Neoplasms/*genetics
MH  - Female
MH  - Gene Dosage
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasms, Adnexal and Skin Appendage/*genetics
MH  - Proto-Oncogene Proteins c-myc/*genetics
MH  - Retinoblastoma Binding Proteins/*genetics
MH  - Sebaceous Gland Neoplasms/*genetics
MH  - Tumor Suppressor Protein p53/*genetics
MH  - Ubiquitin-Protein Ligases/*genetics
PMC - PMC8395148
OTO - NOTNLM
OT  - MYC
OT  - next-generation sequencing
OT  - ocular adnexal tumor
OT  - sebaceous carcinoma
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/28 06:00
MHDA- 2021/09/21 06:00
PMCR- 2021/08/06
CRDT- 2021/08/27 01:23
PHST- 2021/07/12 00:00 [received]
PHST- 2021/08/01 00:00 [revised]
PHST- 2021/08/04 00:00 [accepted]
PHST- 2021/08/27 01:23 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2021/08/06 00:00 [pmc-release]
AID - ijms22168454 [pii]
AID - ijms-22-08454 [pii]
AID - 10.3390/ijms22168454 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Aug 6;22(16):8454. doi: 10.3390/ijms22168454.