PMID- 29461635
OWN - NLM
STAT- MEDLINE
DCOM- 20190910
LR  - 20211204
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 124
IP  - 9
DP  - 2018 May 1
TI  - Clinical and mutational spectrum of highly differentiated, paired box 3:forkhead 
      box protein o1 fusion-negative rhabdomyosarcoma: A report from the Children's 
      Oncology Group.
PG  - 1973-1981
LID - 10.1002/cncr.31286 [doi]
AB  - BACKGROUND: Pediatric paired box 3:forkhead box protein O1 fusion-negative (PF-) 
      rhabdomyosarcoma (RMS) represents a diverse spectrum of tumors with marked 
      differences in histology, myogenic differentiation, and clinical behavior. 
      METHODS: This study sought to evaluate the clinical and mutational spectrum of 24 
      pediatric PF- human RMS tumors with high levels of myogenic differentiation. 
      Tumors were sequenced with OncoPanel v.2, a panel consisting of the coding 
      regions of 504 genes previously linked to human cancer. RESULTS: Most of the 
      tumors (19 of 24) arose at head/neck or genitourinary sites, and the overall 
      survival rate was 100% with a median follow-up time of 4.6 years (range, 1.4-8.6 
      years). RAS pathway gene mutations were the most common mutations in PF-, highly 
      differentiated RMS tumors. In addition, Hedgehog (Hh) and mechanistic target of 
      rapamycin (mTOR) gene mutations with evidence for functional relevance 
      (high-impact) were identified in subsets of tumors. The presence of Hh and mTOR 
      pathway gene mutations was mutually exclusive and was associated with high-impact 
      RAS pathway gene mutations in 3 of 4 Hh-mutated tumors and in 1 of 6 mTOR-mutated 
      tumors. CONCLUSIONS: Interestingly, Hh and mTOR gene mutations were previously 
      associated with rhabdomyomas, which are also known to preferentially arise at 
      head/neck and genitourinary sites. Findings from this study further support the 
      idea that PF-, highly differentiated RMS tumors and rhabdomyomas may represent a 
      continuous spectrum of tumors. Cancer 2018;124:1973-81. (c) 2018 American Cancer 
      Society.
CI  - (c) 2018 American Cancer Society.
FAU - Teot, Lisa A
AU  - Teot LA
AD  - Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.
FAU - Schneider, Michaela
AU  - Schneider M
AD  - Division of Pediatric Hematology and Oncology, Department of Pediatric and 
      Adolescent Medicine, Faculty of Medicine, University of Freiburg, Germany.
FAU - Thorner, Aaron R
AU  - Thorner AR
AD  - Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
FAU - Tian, Jing
AU  - Tian J
AD  - Department of Biostatistics, University of Florida, Gainesville, Florida.
FAU - Chi, Yueh-Yun
AU  - Chi YY
AD  - Department of Biostatistics, University of Florida, Gainesville, Florida.
FAU - Ducar, Matthew
AU  - Ducar M
AD  - Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
FAU - Lin, Ling
AU  - Lin L
AD  - Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
FAU - Wlodarski, Marcin
AU  - Wlodarski M
AD  - Division of Pediatric Hematology and Oncology, Department of Pediatric and 
      Adolescent Medicine, Faculty of Medicine, University of Freiburg, Germany.
FAU - Grier, Holcombe E
AU  - Grier HE
AD  - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, 
      Massachusetts.
FAU - Fletcher, Christopher D M
AU  - Fletcher CDM
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - van Hummelen, Paul
AU  - van Hummelen P
AD  - Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
FAU - Skapek, Stephen X
AU  - Skapek SX
AD  - Division of Hematology/Oncology, Children's Medical Center, University of Texas 
      Southwestern Medical Center, Dallas, Texas.
FAU - Hawkins, Douglas S
AU  - Hawkins DS
AD  - Division of Hematology/Oncology, Seattle Children's Hospital, University of 
      Washington, Seattle, Washington.
AD  - Fred Hutchinson Cancer Center, Seattle, Washington.
FAU - Wagers, Amy J
AU  - Wagers AJ
AD  - Harvard Stem Cell Institute, Cambridge, Massachusetts.
AD  - Department of Stem Cell and Regenerative Biology, Joslin Diabetes Center, Boston, 
      Massachusetts.
AD  - Paul F. Glenn Center for the Biology of Aging at Harvard Medical School, Boston, 
      Massachusetts.
FAU - Rodriguez-Galindo, Carlos
AU  - Rodriguez-Galindo C
AD  - Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, 
      Memphis, Tennessee.
FAU - Hettmer, Simone
AU  - Hettmer S
AUID- ORCID: 0000-0003-1709-4448
AD  - Division of Pediatric Hematology and Oncology, Department of Pediatric and 
      Adolescent Medicine, Faculty of Medicine, University of Freiburg, Germany.
LA  - eng
GR  - U10 CA098413/CA/NCI NIH HHS/United States
GR  - U10 CA098543/CA/NCI NIH HHS/United States
GR  - U10 CA180886/CA/NCI NIH HHS/United States
GR  - U10 CA180899/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180220
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (PAX3-FOXO1A fusion protein, human)
RN  - 0 (Paired Box Transcription Factors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cell Differentiation/genetics
MH  - Child
MH  - Child, Preschool
MH  - DNA Mutational Analysis
MH  - Female
MH  - Follow-Up Studies
MH  - Head and Neck Neoplasms/*genetics/mortality/pathology
MH  - Hedgehog Proteins/genetics
MH  - Humans
MH  - Infant
MH  - Male
MH  - Muscle Cells/pathology
MH  - Muscles/pathology
MH  - Mutation
MH  - Oncogene Proteins, Fusion/genetics
MH  - Paired Box Transcription Factors/genetics
MH  - Rhabdomyosarcoma/*genetics/mortality/pathology
MH  - Signal Transduction/genetics
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases/genetics
MH  - Urogenital Neoplasms/*genetics/mortality/pathology
MH  - Young Adult
MH  - ras Proteins/*genetics/metabolism
PMC - PMC5910184
MID - NIHMS938190
OTO - NOTNLM
OT  - Hedgehog signaling
OT  - RAS
OT  - mechanistic target of rapamycin (mTOR) signaling
OT  - rhabdomyoma
OT  - rhabdomyosarcoma
OT  - sequencing
COIS- Disclosures The authors declare no conflicts of interests. The authors also 
      declare no competing financial interests. Content is solely the responsibility of 
      the authors.
EDAT- 2018/02/21 06:00
MHDA- 2019/09/11 06:00
PMCR- 2019/05/01
CRDT- 2018/02/21 06:00
PHST- 2017/11/01 00:00 [received]
PHST- 2017/12/19 00:00 [revised]
PHST- 2018/01/03 00:00 [accepted]
PHST- 2018/02/21 06:00 [pubmed]
PHST- 2019/09/11 06:00 [medline]
PHST- 2018/02/21 06:00 [entrez]
PHST- 2019/05/01 00:00 [pmc-release]
AID - 10.1002/cncr.31286 [doi]
PST - ppublish
SO  - Cancer. 2018 May 1;124(9):1973-1981. doi: 10.1002/cncr.31286. Epub 2018 Feb 20.