PMID- 27259011
OWN - NLM
STAT- MEDLINE
DCOM- 20170705
LR  - 20181113
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 40
IP  - 10
DP  - 2016 Oct
TI  - Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive 
      Lipofibromatosis-like Neural Tumors.
PG  - 1407-16
LID - 10.1097/PAS.0000000000000675 [doi]
AB  - The family of pediatric fibroblastic and myofibroblastic proliferations 
      encompasses a wide spectrum of pathologic entities with overlapping morphologies 
      and ill-defined genetic abnormalities. Among the superficial lesions, 
      lipofibromatosis (LPF), composed of an admixture of adipose tissue and 
      fibroblastic elements, in the past has been variously classified as infantile 
      fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered 
      a group of superficial soft tissue tumors occurring in children and young adults, 
      with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic 
      atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, 
      suggestive of neural differentiation. SOX10 and melanocytic markers were negative 
      in all cases tested. In contrast, a control group of classic LPF displayed bland, 
      monomorphic histology and lacked S100 protein immunoreactivity. To define the 
      pathogenetic abnormalities in these seemingly distinctive groups, we performed 
      RNA sequencing for fusion gene discovery in 2 cases each, followed by screening 
      for any novel alterations identified in a larger cohort representing both 
      entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and 
      TPM3-NTRK1 gene fusions, which were further validated by fluorescence in situ 
      hybridization (FISH) and reverse transcription polymerase chain reaction. 
      Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene 
      rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each 
      showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs 
      showed NTRK1 gene rearrangements, although regional abnormalities were noted in 
      the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 
      immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but 
      negative in classic LPF. These results suggest that NTRK1 oncogenic activation 
      through gene fusion defines a novel and distinct subset of soft tissue tumors 
      resembling LPF, but displaying cytologic atypia and a neural immunophenotype, 
      provisionally named LPF-like neural tumors.
FAU - Agaram, Narasimhan P
AU  - Agaram NP
AD  - *Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 
      double daggerDepartment of Pathology, Brigham and Women's Hospital, Boston, MA daggerDepartment of 
      Paediatric Laboratory Medicine, Division of Pathology, The Hospital for Sick 
      Children, Toronto, ON, Canada.
FAU - Zhang, Lei
AU  - Zhang L
FAU - Sung, Yun-Shao
AU  - Sung YS
FAU - Chen, Chun-Liang
AU  - Chen CL
FAU - Chung, Catherine T
AU  - Chung CT
FAU - Antonescu, Cristina R
AU  - Antonescu CR
FAU - Fletcher, Christopher Dm
AU  - Fletcher CD
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - P50 CA140146/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Nuclear Pore Complex Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (TPM3 protein, human)
RN  - 0 (TPR protein, human)
RN  - 0 (Tropomyosin)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
CIN - Am J Surg Pathol. 2019 Aug;43(8):1152-1154. PMID: 31107720
MH  - Adolescent
MH  - Adult
MH  - Biomarkers, Tumor/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Fibroma/*genetics/pathology
MH  - Follow-Up Studies
MH  - *Gene Fusion
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lipoma/*genetics/pathology
MH  - Male
MH  - Neoplasms, Complex and Mixed/*genetics/pathology
MH  - Nuclear Pore Complex Proteins/genetics
MH  - Proto-Oncogene Proteins/genetics
MH  - Receptor, trkA/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Soft Tissue Neoplasms/*genetics/pathology
MH  - Tropomyosin/genetics
MH  - Young Adult
PMC - PMC5023452
MID - NIHMS780175
COIS- none
EDAT- 2016/06/04 06:00
MHDA- 2017/07/06 06:00
PMCR- 2017/10/01
CRDT- 2016/06/04 06:00
PHST- 2016/06/04 06:00 [entrez]
PHST- 2016/06/04 06:00 [pubmed]
PHST- 2017/07/06 06:00 [medline]
PHST- 2017/10/01 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000000675 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2016 Oct;40(10):1407-16. doi: 10.1097/PAS.0000000000000675.