STBT5:NTRK-rearranged spindle cell neoplasm (emerging): Difference between revisions

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 ==Genetic Diagnostic Testing Methods==
-''Immunohistochemistry:''  Antibodies have been developed for detection of ''NTRK'' fusions and are being used in clinical laboratories.  Immunohistochemistry has a fast turnaround time, but sensitivity and specificity for detection of ''NTRK'' fusions are lower than other methods listed here.  In sarcomas in particular, false positives can be seen in neural-derived tumors and in tumors harboring ''BCOR'' alterations<ref name=":1" /><ref>{{Cite journal|last=Solomon|first=James P.|last2=Linkov|first2=Irina|last3=Rosado|first3=Andrea|last4=Mullaney|first4=Kerry|last5=Rosen|first5=Ezra Y.|last6=Frosina|first6=Denise|last7=Jungbluth|first7=Achim A.|last8=Zehir|first8=Ahmet|last9=Benayed|first9=Ryma|date=2020-01|title=NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls|url=https://pubmed.ncbi.nlm.nih.gov/31375766|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=33|issue=1|pages=38–46|doi=10.1038/s41379-019-0324-7|issn=1530-0285|pmc=7437403|pmid=31375766}}</ref><ref>{{Cite journal|last=Hung|first=Yin P.|last2=Fletcher|first2=Christopher D. M.|last3=Hornick|first3=Jason L.|date=2018-10|title=Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics|url=https://pubmed.ncbi.nlm.nih.gov/29863809|journal=Histopathology|volume=73|issue=4|pages=634–644|doi=10.1111/his.13666|issn=1365-2559|pmid=29863809}}</ref><ref>{{Cite journal|last=Kao|first=Yu-Chien|last2=Sung|first2=Yun-Shao|last3=Argani|first3=Pedram|last4=Swanson|first4=David|last5=Alaggio|first5=Rita|last6=Tap|first6=William|last7=Wexler|first7=Leonard|last8=Dickson|first8=Brendan C.|last9=Antonescu|first9=Cristina R.|date=2020-07|title=NTRK3 overexpression in undifferentiated sarcomas with YWHAE and BCOR genetic alterations|url=https://pubmed.ncbi.nlm.nih.gov/32034283|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=33|issue=7|pages=1341–1349|doi=10.1038/s41379-020-0495-2|issn=1530-0285|pmc=7329614|pmid=32034283}}</ref>.  Confirmatory testing with other molecular-based methods is recommended.
+'''Immunohistochemistry'''
+* Antibodies have been developed for detection of ''NTRK'' fusions and are being used in clinical laboratories.
+* Immunohistochemistry has a fast turnaround time, but sensitivity and specificity for detection of ''NTRK'' fusions are lower than other methods listed here.
+* In sarcomas in particular, false positives can be seen in neural-derived tumors and in tumors harboring ''BCOR'' alterations<ref name=":1" /><ref>{{Cite journal|last=Solomon|first=James P.|last2=Linkov|first2=Irina|last3=Rosado|first3=Andrea|last4=Mullaney|first4=Kerry|last5=Rosen|first5=Ezra Y.|last6=Frosina|first6=Denise|last7=Jungbluth|first7=Achim A.|last8=Zehir|first8=Ahmet|last9=Benayed|first9=Ryma|date=2020-01|title=NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls|url=https://pubmed.ncbi.nlm.nih.gov/31375766|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=33|issue=1|pages=38–46|doi=10.1038/s41379-019-0324-7|issn=1530-0285|pmc=7437403|pmid=31375766}}</ref><ref>{{Cite journal|last=Hung|first=Yin P.|last2=Fletcher|first2=Christopher D. M.|last3=Hornick|first3=Jason L.|date=2018-10|title=Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics|url=https://pubmed.ncbi.nlm.nih.gov/29863809|journal=Histopathology|volume=73|issue=4|pages=634–644|doi=10.1111/his.13666|issn=1365-2559|pmid=29863809}}</ref><ref>{{Cite journal|last=Kao|first=Yu-Chien|last2=Sung|first2=Yun-Shao|last3=Argani|first3=Pedram|last4=Swanson|first4=David|last5=Alaggio|first5=Rita|last6=Tap|first6=William|last7=Wexler|first7=Leonard|last8=Dickson|first8=Brendan C.|last9=Antonescu|first9=Cristina R.|date=2020-07|title=NTRK3 overexpression in undifferentiated sarcomas with YWHAE and BCOR genetic alterations|url=https://pubmed.ncbi.nlm.nih.gov/32034283|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=33|issue=7|pages=1341–1349|doi=10.1038/s41379-020-0495-2|issn=1530-0285|pmc=7329614|pmid=32034283}}</ref>.  Confirmatory testing with other molecular-based methods is recommended.
-''Fluorescent in situ hybridization (FISH)'':  Breakapart probes for ''NTRK1, NTRK2,'' and ''NTRK3'' can identify breaks in these genes, although the probes not widely available in clinical laboratories.  Benefits of this approach include high sensitivity, particularly in samples with low tumor content, fast turnaround time, and only require a few unstained slides.  This approach does not allow for identification of the fusion partner nor for a detailed evaluation of oncogenicity.
-''Reverse transcriptase polymerase chain reaction (RT-PCR)'' can only identify specific fusion pairs (e.g. ''ETV6::NTRK3''), such that alternate pairings will be missed. '' ''With the availability of RNA-based sequencing, this technique is now rarely used clinically.
+'''''Fluorescent in situ hybridization (FISH)'''''
+* Breakapart probes for ''NTRK1, NTRK2,'' and ''NTRK3'' can identify breaks in these genes, although the probes not widely available in clinical laboratories.
+* Benefits of this approach include high sensitivity, particularly in samples with low tumor content, fast turnaround time, and only require a few unstained slides.
+* This approach does not allow for identification of the fusion partner nor for a detailed evaluation of oncogenicity.'
-''RNA-based sequencing'' is becoming widely used for comprehensive fusion detection.  It is often performed as a comprehensive panel, so ''NTRK'' fusions can be assessed at the same time as many other sarcoma-associated fusions.  A platform that supports fusion detection in a partner agnostic manner such as anchored multiplex PCR or hybridization capture methods is preferred<ref>{{Cite journal|last=Amatu|first=A.|last2=Sartore-Bianchi|first2=A.|last3=Bencardino|first3=K.|last4=Pizzutilo|first4=E. G.|last5=Tosi|first5=F.|last6=Siena|first6=S.|date=2019-11-01|title=Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer|url=https://pubmed.ncbi.nlm.nih.gov/31738427|journal=Annals of Oncology: Official Journal of the European Society for Medical Oncology|volume=30|issue=Suppl_8|pages=viii5–viii15|doi=10.1093/annonc/mdz383|issn=1569-8041|pmc=6859819|pmid=31738427}}</ref>.  A systematic approach should be used to assess oncogenicity of ''NTRK'' fusions including stranding and directionality, inclusion of the kinase domain, and review of the literature<ref>{{Cite journal|last=Saliba|first=Jason|last2=Church|first2=Alanna J.|last3=Rao|first3=Shruti|last4=Danos|first4=Arpad|last5=Furtado|first5=Larissa V.|last6=Laetsch|first6=Theodore|last7=Zhang|first7=Liying|last8=Nardi|first8=Valentina|last9=Lin|first9=Wan-Hsin|date=2022-06|title=Standardized evidence-based approach for assessment of oncogenic and clinical significance of NTRK fusions|url=https://pubmed.ncbi.nlm.nih.gov/35366592|journal=Cancer Genetics|volume=264-265|pages=50–59|doi=10.1016/j.cancergen.2022.03.001|issn=2210-7762|pmc=9252326|pmid=35366592}}</ref>.
+'''''Reverse transcriptase polymerase chain reaction (RT-PCR)'''''
+* Can only identify specific fusion pairs (e.g. ''ETV6::NTRK3''), such that alternate pairings will be missed. '' ''
+* With the availability of RNA-based sequencing, this technique is now rarely used clinically.
+'''''RNA-based sequencing'''''
+* Becoming widely used for comprehensive fusion detection.  It is often performed as a comprehensive panel, so ''NTRK'' fusions can be assessed at the same time as many other sarcoma-associated fusions.
+* A platform that supports fusion detection in a partner agnostic manner such as anchored multiplex PCR or hybridization capture methods is preferred<ref>{{Cite journal|last=Amatu|first=A.|last2=Sartore-Bianchi|first2=A.|last3=Bencardino|first3=K.|last4=Pizzutilo|first4=E. G.|last5=Tosi|first5=F.|last6=Siena|first6=S.|date=2019-11-01|title=Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer|url=https://pubmed.ncbi.nlm.nih.gov/31738427|journal=Annals of Oncology: Official Journal of the European Society for Medical Oncology|volume=30|issue=Suppl_8|pages=viii5–viii15|doi=10.1093/annonc/mdz383|issn=1569-8041|pmc=6859819|pmid=31738427}}</ref>.
+* A systematic approach should be used to assess oncogenicity of ''NTRK'' fusions including stranding and directionality, inclusion of the kinase domain, and review of the literature<ref>{{Cite journal|last=Saliba|first=Jason|last2=Church|first2=Alanna J.|last3=Rao|first3=Shruti|last4=Danos|first4=Arpad|last5=Furtado|first5=Larissa V.|last6=Laetsch|first6=Theodore|last7=Zhang|first7=Liying|last8=Nardi|first8=Valentina|last9=Lin|first9=Wan-Hsin|date=2022-06|title=Standardized evidence-based approach for assessment of oncogenic and clinical significance of NTRK fusions|url=https://pubmed.ncbi.nlm.nih.gov/35366592|journal=Cancer Genetics|volume=264-265|pages=50–59|doi=10.1016/j.cancergen.2022.03.001|issn=2210-7762|pmc=9252326|pmid=35366592}}</ref>.
 ==Familial Forms==