Tyrosine kinase‐altered spindle cell neoplasms with <scp><i>EGFR</i></scp> internal tandem duplications

Kao, Ellen; Pinto, Navin; Trobaugh‐Lotrario, Angela D.; Deutsch, Gail H.; Wu, Yu Chung; Wang, Wenjing; Rudzinski, Erin R.; Liu, Yajuan J.

doi:10.1002/gcc.23067

Cited by 6 publications

(2 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[5][6][7][8] Very recently, EGFR TKDD has also been reported in infantile spindle cell tumors. [14][15][16] FGFR1 activation driven by TKDD found in our case further broadens the molecular spectrum of pediatric spindle cell tumors.…”

Section: Meanwhile Cancer Genome Profiling Of Her Tumor Specimen Withsupporting

confidence: 60%

FGFR1 tyrosine kinase domain duplication in infantile soft tissue spindle cell tumor

Akahane

Kasai

Watanabe

et al. 2023

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Section: Meanwhile Cancer Genome Profiling Of Her Tumor Specimen Withsupporting

confidence: 60%

FGFR1 tyrosine kinase domain duplication in infantile soft tissue spindle cell tumor

Akahane

Kasai

Watanabe

et al. 2023

Pediatric Blood & Cancer

View full text Add to dashboard Cite

“…Similarly, EGFR ITDs are described in the setting of infantile fibrosarcoma and congenital mesoblastic nephroma, particularly in classic or mixed subtype, and aids in diagnostics if the tumor is negative for the more commonly identified ETV6::NTRK3 fusion. This scenario further highlights the utility of broader panel testing and analysis to encompass recurrent events to enable alignment for an integrated diagnosis along with histopathologic characteris-tics [19,20,37,61]. FGFR1 ITDs are commonly reported in the setting of low-grade glial tumors for which the therapeutic significance is still under study [5,8,15].…”

Section: Discussionmentioning

confidence: 97%

Expanding the Clinical Utility of Targeted RNA Sequencing Panels beyond Gene Fusions to Complex, Intragenic Structural Rearrangements

Schieffer,

Moccia,

Bucknor

et al. 2023

Cancers

View full text Add to dashboard Cite

Gene fusions are a form of structural rearrangement well established as driver events in pediatric and adult cancers. The identification of such events holds clinical significance in the refinement, prognostication, and provision of treatment in cancer. Structural rearrangements also extend beyond fusions to include intragenic rearrangements, such as internal tandem duplications (ITDs) or exon-level deletions. These intragenic events have been increasingly implicated as cancer-promoting events. However, the detection of intragenic rearrangements may be challenging to resolve bioinformatically with short-read sequencing technologies and therefore may not be routinely assessed in panel-based testing. Within an academic clinical laboratory, over three years, a total of 608 disease-involved samples (522 hematologic malignancy, 86 solid tumors) underwent clinical testing using Anchored Multiplex PCR (AMP)-based RNA sequencing. Hematologic malignancies were evaluated using a custom Pan-Heme 154 gene panel, while solid tumors were assessed using a custom Pan-Solid 115 gene panel. Gene fusions, ITDs, and intragenic deletions were assessed for diagnostic, prognostic, or therapeutic significance. When considering gene fusions alone, we report an overall diagnostic yield of 36% (37% hematologic malignancy, 41% solid tumors). When including intragenic structural rearrangements, the overall diagnostic yield increased to 48% (48% hematologic malignancy, 45% solid tumor). We demonstrate the clinical utility of reporting structural rearrangements, including gene fusions and intragenic structural rearrangements, using an AMP-based RNA sequencing panel.

show abstract

Pediatric Fibromatosis Lacks the Internal Tandem Duplication of EGFR Seen in Congenital Mesoblastic Nephroma

Chami,

Marrano,

Thorner

2024

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Classical and mixed congenital mesoblastic nephroma (CMN) are characterized by an internal tandem duplication (ITD) of the EGFR gene, in contrast to cellular CMN that usually harbors an ETV6::NTRK3 gene fusion. This same fusion occurs in infantile fibrosarcoma, and this tumor can be considered as the soft tissue equivalent of cellular CMN. A soft tissue equivalent of classic/mixed CMN remains undefined at the genetic level. Since classical CMN resembles fibromatosis of soft tissue histologically, we asked whether fibromatosis in children might show EGFR ITD. ITD was investigated using the polymerase chain reaction and primers for exons 18 and 25 of the EGFR gene. Seven of the eight cases of classical or mixed CMN were positive by this approach, but none of the five cellular CMNs. Of 11 cases of fibromatosis (six plantar, two digital, and three desmoid), none were positive for EGFR ITD. Within the limits of this small study, we conclude that pediatric fibromatosis is likely not characterized by EGFR ITD. There are isolated reports of pediatric soft tissue tumors that harbor EGFR ITD, but these have the appearance of infantile fibrosarcoma or mixed CMN rather than fibromatosis. We did not find any such cases, since all 14 cases of infantile fibrosarcoma in our study had an ETV6::NTRK3 fusion. The soft tissue tumors with EGFR ITD are not a morphologic match for the low‐grade histology of classical CMN. Whether they have a similar favorable biology or behave more like fibrosarcoma with an ETV6::NTRK3 fusion or an alternative fusion involving other kinases remains to be determined.

show abstract

Tyrosine kinase‐altered spindle cell neoplasms with EGFR internal tandem duplications

Cited by 6 publications

References 15 publications

FGFR1 tyrosine kinase domain duplication in infantile soft tissue spindle cell tumor

FGFR1 tyrosine kinase domain duplication in infantile soft tissue spindle cell tumor

Expanding the Clinical Utility of Targeted RNA Sequencing Panels beyond Gene Fusions to Complex, Intragenic Structural Rearrangements

Pediatric Fibromatosis Lacks the Internal Tandem Duplication of EGFR Seen in Congenital Mesoblastic Nephroma

Contact Info

Product

Resources

About