PMID- 33072748
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201020
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 8
DP  - 2020
TI  - Intratumoral Translocation Positive Heterogeneity in Pediatric Alveolar 
      Rhabdomyosarcoma Tumors Correlates to Patient Survival Prognosis.
PG  - 564136
LID - 10.3389/fcell.2020.564136 [doi]
LID - 564136
AB  - Alveolar rhabdomyosarcoma (ARMS) is characterized by one of three translocation 
      states: t(2;13) (q35;q14) producing PAX3-FOXO1, t(1;13) (p36;q14) producing 
      PAX7-FOXO1, or translocation-negative. Tumors with t(2;13) are associated with 
      greater disease severity and mortality than t(1;13) positive or translocation 
      negative patients. Consistent with this fact, previous work concluded that a 
      molecular analysis of RMS translocation status is essential for the accurate 
      determination of prognosis and diagnosis. However, despite this knowledge, most 
      diagnoses rely on histology and in some cases utilize fluorescence in situ 
      hybridization (FISH) probes unable to differentiate between translocation 
      products. Along these same lines, diagnostic RT-PCR analysis, which can 
      differentiate translocation status, is unable to determine intratumoral 
      translocation heterogeneity, making it difficult to determine if heterogeneity 
      exists and whether correlations exist between this heterogeneity and patient 
      outcomes. Using newly developed FISH probes, we demonstrate that intratumoral 
      heterogeneity exists in ARMS tumors with respect to the presence or absence of 
      the translocation product. We found between 3 and 98% of cells within individual 
      tumor samples contained a translocation event with a significant inverse 
      correlation (R (2) = 0.66, p = 0.001) between the extent of intratumoral 
      translocation heterogeneity and failure-free survival of patients. Taken 
      together, these results provide additional support for the inclusion of the 
      molecular analysis of these tumors and expand on this idea to support determining 
      the extent of intratumoral translocation heterogeneity in the diagnosis of ARMS 
      to improve diagnostic and prognostic indicators for patients with these tumors.
CI  - Copyright (c) 2020 Gleditsch, Penas, Mercer, Umrigar, Briscoe, Stark, Tsien and 
      Hollenbach.
FAU - Gleditsch, Katrina
AU  - Gleditsch K
AD  - Department of Genetics, Louisiana State University Health Sciences Center, New 
      Orleans, LA, United States.
AD  - Division of Pediatric Hematology/Oncology, Children's Hospital of New Orleans, 
      New Orleans, LA, United States.
FAU - Penas, Jorge
AU  - Penas J
AD  - Department of Genetics, Louisiana State University Health Sciences Center, New 
      Orleans, LA, United States.
FAU - Mercer, Danielle
AU  - Mercer D
AD  - Department of Genetics, Louisiana State University Health Sciences Center, New 
      Orleans, LA, United States.
FAU - Umrigar, Ayesha
AU  - Umrigar A
AD  - Department of Genetics, Louisiana State University Health Sciences Center, New 
      Orleans, LA, United States.
FAU - Briscoe, James
AU  - Briscoe J
AD  - Department of Genetics, Louisiana State University Health Sciences Center, New 
      Orleans, LA, United States.
FAU - Stark, Matthew
AU  - Stark M
AD  - Department of Pathology, Children's Hospital of New Orleans, New Orleans, LA, 
      United States.
FAU - Tsien, Fern
AU  - Tsien F
AD  - Department of Genetics, Louisiana State University Health Sciences Center, New 
      Orleans, LA, United States.
FAU - Hollenbach, Andrew D
AU  - Hollenbach AD
AD  - Department of Genetics, Louisiana State University Health Sciences Center, New 
      Orleans, LA, United States.
LA  - eng
PT  - Journal Article
DEP - 20200918
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC7530338
OTO - NOTNLM
OT  - Alveolar rhabdomyosarcoma
OT  - Pax3-FOXO1
OT  - molecular genetics
OT  - prognostic outcome
OT  - tumor heterogeneity
EDAT- 2020/10/20 06:00
MHDA- 2020/10/20 06:01
PMCR- 2020/01/01
CRDT- 2020/10/19 05:59
PHST- 2020/05/20 00:00 [received]
PHST- 2020/09/01 00:00 [accepted]
PHST- 2020/10/19 05:59 [entrez]
PHST- 2020/10/20 06:00 [pubmed]
PHST- 2020/10/20 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2020.564136 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2020 Sep 18;8:564136. doi: 10.3389/fcell.2020.564136. 
      eCollection 2020.