STBT5:Infantile fibrosarcoma: Difference between revisions - Compendium of Cancer Genome Aberrations

(One intermediate revision by the same user not shown)

Line 2:

[[STBT5:Table_of_Contents|Soft Tissue and Bone Tumours (Who Classification, 5th ed.)]]

~~{{Under Construction}}~~

(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ HUGO-approved gene names and symbols] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' ''[[Author_Instructions]]'' ''and [[Frequently Asked Questions (FAQs)|FAQs]] as well as contact your [[Leadership|Associate Editor]] or [mailto:CCGA@cancergenomics.org Technical Support].)''

==Primary Author(s)*==

Kathleen Schieffer, PhD, FACMG

Line 42:

Line 38:

==Gene Rearrangements==

Put your text here and fill in the table (''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')

{| class="wikitable sortable"

|-

Line 68:

Line 63:

|''NTRK1''

|''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" />

|None

|Recurrent

Line 85:

Line 80:

|-

|''BRAF''

|''~~PT7~~, CUX1''

|''SEPT7, CUX1''

|

|In-frame fusion that is predicted to result in activation of the BRAF tyrosine kinase domain.<ref name=":12" />

|None

|Rare

|

|D

|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''

Line 98:

Line 93:

|None

|Rare

|

|D

|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''

|''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

|Rare

|

|D

|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''

Line 121:

Line 116:

|}

==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"

|-

Line 173:

Line 168:

!Clinical Relevance Details/Other Notes

|-

|

|N/A

|

|N/A

|

|N/A

|

|N/A

|

|N/A

|

|N/A

|}

==Gene Mutations (SNV/INDEL)==

Line 190:

Line 185:

!Clinical Relevance Details/Other Notes

|-

|

|N/A

|

|N/A

|

|N/A

|

|N/A

|

|N/A

|

|N/A

|

|N/A

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ cBioportal], [https://cancer.sanger.ac.uk/cosmic COSMIC], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

==Epigenomic Alterations==

None

==Genes and Main Pathways Involved==

~~Put your text here and fill in the table (''Instructions: Please include references throughout the table. Do not delete the table.)''~~

{| class="wikitable sortable"

|-

Line 212:

Line 206:

==Genetic Diagnostic Testing Methods==

*Fusion testing

#'''Fusion testing'''

**Targeted sequencing (such as RT-PCR or targeted next-generation sequencing (NGS) panels)

#*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

#**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

#*Whole transcriptome RNA-sequencing

***Provides an unbiased approach to fusion calling

#**Provides an unbiased approach to fusion calling

*Fluorescence ''in situ'' hybridization (FISH)

#'''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.

#*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

#'''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)

#*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

#'''DNA sequencing'''

**Can identify the commonly reported aneusomies if copy number variant calling is performed

#*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

#*Currently, there are no recurrently described somatic SNV/indels for infantile fibrosarcoma

==Familial Forms==

Line 230:

Line 224:

None

==Links==

Put a link here or anywhere appropriate in this page (''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')

None

==References==

~~(use the "Cite" icon at the top of the page) (''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''''.'')~~</~~span~~>

[[Category:STBT5]]

[[Category:DISEASE]]

[[Category:Diseases I]]

==Notes==

<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''Associate Editor'']] or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

~~Prior Author(s):~~

<nowiki>*</nowiki>''Citation of this Page'': “Infantile fibrosarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/STBT5:Infantile fibrosarcoma</nowiki>.

~~[[Category:STBT5]]~~

~~[[Category:DISEASE]]~~

~~[[Category:Diseases I]]~~

~~<references />~~

@@ Line 2: / Line 2: @@
 [[STBT5:Table_of_Contents|Soft Tissue and Bone Tumours (Who Classification, 5th ed.)]]
-{{Under Construction}}
-<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
 ==Primary Author(s)*==
 Kathleen Schieffer, PhD, FACMG
@@ Line 42: / Line 38: @@
 ==Gene Rearrangements==
-Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 {| class="wikitable sortable"
 |-
@@ Line 68: / Line 63: @@
 |''NTRK1''
 |''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" />
 |None
 |Recurrent
@@ Line 85: / Line 80: @@
 |-
 |''BRAF''
-|''PT7, CUX1''
+|''SEPT7, CUX1''
-|
+|In-frame fusion that is predicted to result in activation of the BRAF tyrosine kinase domain.<ref name=":12" />
 |None
 |Rare
-|
+|D
 |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''
@@ Line 98: / Line 93: @@
 |None
 |Rare
-|
+|D
 |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''
 |''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
 |Rare
-|
+|D
 |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''
@@ Line 121: / Line 116: @@
 |}
 ==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"
 |-
@@ Line 173: / Line 168: @@
 !Clinical Relevance Details/Other Notes
 |-
-|
+|N/A
-|
+|N/A
-|
+|N/A
-|
+|N/A
-|
+|N/A
-|
+|N/A
 |}
 ==Gene Mutations (SNV/INDEL)==
@@ Line 190: / Line 185: @@
 !Clinical Relevance Details/Other Notes
 |-
-|
+|N/A
-|
+|N/A
-|
+|N/A
-|
+|N/A
-|
+|N/A
-|
+|N/A
-|
+|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.
 ==Epigenomic Alterations==
 None
 ==Genes and Main Pathways Involved==
-Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
 {| class="wikitable sortable"
 |-
@@ Line 212: / Line 206: @@
 ==Genetic Diagnostic Testing Methods==
-*Fusion testing
+#'''Fusion testing'''
-**Targeted sequencing (such as RT-PCR or targeted next-generation sequencing (NGS) panels)
+#*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
+#**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
+#*Whole transcriptome RNA-sequencing
-***Provides an unbiased approach to fusion calling
+#**Provides an unbiased approach to fusion calling
-*Fluorescence ''in situ'' hybridization (FISH)
+#'''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.
+#*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
+#'''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)
+#*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
+#'''DNA sequencing'''
-**Can identify the commonly reported aneusomies if copy number variant calling is performed
+#*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
+#*Currently, there are no recurrently described somatic SNV/indels for infantile fibrosarcoma
 ==Familial Forms==
@@ Line 230: / Line 224: @@
 None
 ==Links==
-Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
+None
 ==References==
-(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
+[[Category:STBT5]]
+[[Category:DISEASE]]
+[[Category:Diseases I]]
+<references />
 ==Notes==
 <nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
-Prior Author(s):
 <nowiki>*</nowiki>''Citation of this Page'': “Infantile fibrosarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/STBT5:Infantile fibrosarcoma</nowiki>.
-[[Category:STBT5]]
-[[Category:DISEASE]]
-[[Category:Diseases I]]
-<references />