STBT5:Infantile fibrosarcoma: Difference between revisions
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|''NTRK1'' | |''NTRK1'' | ||
|''LMNA, TPM3, SQSTM1, MIR584F1'' | |''LMNA, TPM3, SQSTM1, MIR584F1'' | ||
|In-frame fusion that is predicted to result in constitutive activation of the NTRK1 tyrosine kinase domain likely through dimerization of the 5' fusion partner.<ref name=":1" /> | |In-frame fusion that is predicted to result in constitutive activation of the NTRK1 tyrosine kinase domain likely through dimerization of the 5' fusion partner.<ref name=":1" /> | ||
|None | |None | ||
|Recurrent | |Recurrent | ||
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|- | |- | ||
|''BRAF'' | |''BRAF'' | ||
|'' | |''SEPT7, CUX1'' | ||
| | |In-frame fusion that is predicted to result in activation of the BRAF tyrosine kinase domain.<ref name=":12" /> | ||
|None | |None | ||
|Rare | |Rare | ||
| | |D | ||
|No | |No | ||
| | |Five individuals with unclassified spindle cell sarcomas with features overlapping infantile fibrosarcoma were identified as having a ''BRAF'' rearrangement. ''BRAF'' rearrangement was identified by FISH in 3 patients, while a ''SEPT7::BRAF'' and ''CUX1::BRAF'' fusion were observed in an additional 2 tumors using next generation sequencing.<ref name=":12" /> Although ''BRAF'' fusions are targetable in other tumor types, the utility of targeted therapy in this setting requires further study. | ||
|- | |- | ||
|''BRAF'' | |''BRAF'' | ||
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|None | |None | ||
|Rare | |Rare | ||
| | |D | ||
|No | |No | ||
| | |An intragenic rearrangement within ''BRAF'' was identified in a single individual with infantile fibrosarcoma.<ref name=":3" /> Although ''BRAF'' fusions are targetable in other tumor types, the utility of targeted therapy in this setting requires further study. | ||
|- | |- | ||
|''RET'' | |''RET'' | ||
|''CLIP2, MYH10'' | |''CLIP2, MYH10'' | ||
| | |In-frame fusion that is predicted to result in activation of the BRAF tyrosine kinase domain. All reported cases demonstrated a breakpoint in exon 12 of ''RET'' (NM_020975.4), retaining the entire tyrosine kinase domain. | ||
|None | |None | ||
|Rare | |Rare | ||
| | |D | ||
|No | |No | ||
| | |SIx patients in total have been reported with a tumor demonstrating IFS-like histology and a ''RET'' fusion (''CLIP2'' n=2, ''MYH10'' n=4).<ref>{{Cite journal|last=Davis|first=Jessica L.|last2=Vargas|first2=Sara O.|last3=Rudzinski|first3=Erin R.|last4=López Marti|first4=Jessica M.|last5=Janeway|first5=Katherine|last6=Forrest|first6=Suzanne|last7=Winsnes|first7=Katrina|last8=Pinto|first8=Navin|last9=Yang|first9=Sung E.|date=2020-06|title=Recurrent RET gene fusions in paediatric spindle mesenchymal neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/31994201|journal=Histopathology|volume=76|issue=7|pages=1032–1041|doi=10.1111/his.14082|issn=1365-2559|pmid=31994201}}</ref><ref>{{Cite journal|last=Antonescu|first=Cristina R.|last2=Dickson|first2=Brendan C.|last3=Swanson|first3=David|last4=Zhang|first4=Lei|last5=Sung|first5=Yun-Shao|last6=Kao|first6=Yu-Chien|last7=Chang|first7=Wei-Chin|last8=Ran|first8=Leili|last9=Pappo|first9=Alberto|date=2019-10|title=Spindle Cell Tumors With RET Gene Fusions Exhibit a Morphologic Spectrum Akin to Tumors With NTRK Gene Fusions|url=https://pubmed.ncbi.nlm.nih.gov/31219820|journal=The American Journal of Surgical Pathology|volume=43|issue=10|pages=1384–1391|doi=10.1097/PAS.0000000000001297|issn=1532-0979|pmc=6742579|pmid=31219820}}</ref> The utility of RET targeted therapy in this setting requires further study. | ||
|- | |- | ||
|''MET'' | |''MET'' | ||
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|} | |} | ||
==Individual Region Genomic Gain/Loss/LOH== | ==Individual Region Genomic Gain/Loss/LOH== | ||
Whole chromosome gain of 8, 11, 17, and 20 (in various combinations) are commonly observed in infantile fibrosarcoma. | Whole chromosome gain of 8, 11, 17, and/or 20 (in various combinations) are commonly observed in infantile fibrosarcoma. Copy number findings alone and in the absence of appropriate histopathology and/or diagnostic gene fusion are not diagnostic, prognostic, or therapeutic. | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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!Clinical Relevance Details/Other Notes | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
|} | |} | ||
==Gene Mutations (SNV/INDEL)== | ==Gene Mutations (SNV/INDEL)== | ||
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!Clinical Relevance Details/Other Notes | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
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| | |N/A | ||
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | |}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | ||
==Epigenomic Alterations== | ==Epigenomic Alterations== | ||
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==Genetic Diagnostic Testing Methods== | ==Genetic Diagnostic Testing Methods== | ||
#'''Fusion testing''' | |||
#*Targeted sequencing (such as RT-PCR or targeted next-generation sequencing (NGS) panels) | |||
#**For targeted NGS panels, consider if the assay requires both gene partners to be included on the panel or if it is able to identify novel fusions as long as one of the partners is included on the panel | |||
#*Whole transcriptome RNA-sequencing | |||
#**Provides an unbiased approach to fusion calling | |||
#'''Fluorescence ''in situ'' hybridization (FISH)''' | |||
#*Break apart probes for ''ETV6'' and/or ''NTRK3'' will identify a rearrangement (''ETV6::NTRK3'') present in the majority of infantile fibrosarcoma. Consider other fusion partners is ''ETV6'' FISH is negative. | |||
#'''Karyotyping''' | |||
#*Can identify the t(12;15) rearrangement as well as other commonly reported aneusomies (i.e. whole chromosome gains of 8, 11, 17, 20) | |||
#'''DNA sequencing''' | |||
#*Can identify the commonly reported aneusomies if copy number variant calling is performed | |||
#*Currently, there are no recurrently described somatic SNV/indels for infantile fibrosarcoma | |||
==Familial Forms== | ==Familial Forms== | ||