The value of GLI1 and p16 immunohistochemistry in the premolecular screening for GLI1-altered mesenchymal neoplasms

Machado, Isidro; Agaimy, Abbas; Giner, Francisco; Navarro, Samuel; Michal, Michael; Bridge, Julia; Claramunt, Reyes; López-Guerrero, José Antonio; Alcacer, Javier; Linos, Konstantinos; Llombart-Bosch, Antonio

doi:10.1007/s00428-023-03687-3

Cited by 6 publications

(11 citation statements)

References 33 publications

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“…CDK4 gene amplification in sarcomas has been observed in both bone and soft tissue tumors, while MDM2 gene amplification predominates in soft tissue tumors, often without coamplification of other genes in the 12q13-q15 region [77,[91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108].…”

Section: Does Isolated Mdm2 Cdk4 or Gli1 Amplification Matter Vs Chro...mentioning

confidence: 99%

“…In a group of soft tissue tumors with shared morphological characteristics, two genetic alterations in GLI1 have been described: GLI1 fusions (in a low frequency of cases studied) and high-level amplifications, often coamplified with neighboring genes in the 12q13.3-q15 region, such as DDIT3/CDK4/MDM2/STAT6 genes [75][76][77][78][79][80][81][104][105][106][107][108].…”

Section: Does Isolated Mdm2 Cdk4 or Gli1 Amplification Matter Vs Chro...mentioning

confidence: 99%

“…On the other hand, the DDIT3 gene is known to be rearranged in myxoid/round cell liposarcomas, which can fuse with either EWSR1 or FUS, and these fusions serve as diagnostic markers for this entity [112]. The amplification of DDIT3 and STAT6 may vary depending on the amplicon length in cases of mesenchymal neoplasms with 12q13-15 amplification [101][102][103][104][105][106][107][108][109][110][111][112][113][114][115].…”

Section: Implications Of Detecting Isolated Mdm2-cdk4-gli1 Alteration...mentioning

confidence: 99%

“…Recently, a group of mesenchymal neoplasms with predominantly epithelioid morphology has been described [75][76][77][78][79][80][81][104][105][106][107][108]. These neoplasms typically express CD56, S100, and p16 and are predominantly located in the head and neck region, displaying alterations in the GLI1 gene.…”

Section: Implications Of Detecting Isolated Mdm2-cdk4-gli1 Alteration...mentioning

confidence: 99%

“…GLI1 is situated in the 12q13.3 region, in close proximity to the genes within the 12q13-15 region, particularly DDIT3. Neoplasms with GLI1 alterations may exhibit either GLI1 rearrangements or amplifications of this gene [75][76][77][78][79][80][81][104][105][106][107][108].…”

Section: Implications Of Detecting Isolated Mdm2-cdk4-gli1 Alteration...mentioning

confidence: 99%

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Soft Tissue Sarcomas with Chromosomal Alterations in the 12q13-15 Region: Differential Diagnosis and Therapeutic Implications

Lavernia,

Claramunt,

Romero

et al. 2024

Cancers

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The chromosomal region 12q13-15 is rich in oncogenes and contains several genes involved in the pathogenesis of various mesenchymal neoplasms. Notable genes in this region include MDM2, CDK4, STAT6, DDIT3, and GLI1. Amplification of MDM2 and CDK4 genes can be detected in various mesenchymal and nonmesenchymal neoplasms. Therefore, gene amplification alone is not entirely specific for making a definitive diagnosis and requires the integration of clinical, radiological, morphological, and immunohistochemical findings. Neoplasms with GLI1 alterations may exhibit either GLI1 rearrangements or amplifications of this gene. Despite the diagnostic implications that the overlap of genetic alterations in neoplasms with changes in genes within the 12q13-15 region could create, the discovery of coamplifications of MDM2 with CDK4 and GLI1 offers new therapeutic targets in neoplasms with MDM2/CDK4 amplification. Lastly, it is worth noting that MDM2 or CDK4 amplification is not exclusive to mesenchymal neoplasms; this genetic alteration has also been observed in other epithelial neoplasms or melanomas. This suggests the potential use of MDM2 or CDK4 inhibitors in neoplasms where alterations in these genes do not aid the pathological diagnosis but may help identify potential therapeutic targets. In this review, we delve into the diagnosis and therapeutic implications of tumors with genetic alterations involving the chromosomal region 12q13-15, mainly MDM2, CDK4, and GLI1.

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Section: Does Isolated Mdm2 Cdk4 or Gli1 Amplification Matter Vs Chro...mentioning

confidence: 99%

Section: Does Isolated Mdm2 Cdk4 or Gli1 Amplification Matter Vs Chro...mentioning

confidence: 99%

Section: Implications Of Detecting Isolated Mdm2-cdk4-gli1 Alteration...mentioning

confidence: 99%

Section: Implications Of Detecting Isolated Mdm2-cdk4-gli1 Alteration...mentioning

confidence: 99%

Section: Implications Of Detecting Isolated Mdm2-cdk4-gli1 Alteration...mentioning

confidence: 99%

See 3 more Smart Citations

Soft Tissue Sarcomas with Chromosomal Alterations in the 12q13-15 Region: Differential Diagnosis and Therapeutic Implications

Lavernia,

Claramunt,

Romero

et al. 2024

Cancers

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Gastroblastoma with a novel ACTB::GLI1 gene fusion in a 19-year-old male

Shabbir,

Earle,

Glomski

et al. 2024

Virchows Arch

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Molecularly defined sinonasal malignancies: an overview with focus on the current WHO classification and recently described provisional entities

Skálová,

Agaimy,

Bradova

et al. 2024

Virchows Arch

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Classification of tumors of the head and neck has evolved in recent decades including a widespread application of molecular testing in tumors of the sinonasal tract, salivary glands, and soft tissues with a predilection for the head and neck. The availability of new molecular techniques has allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, an expanding spectrum of immunohistochemical markers specific to genetic alterations facilitates rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined tumor classification while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review covers the principal molecular alterations in sinonasal malignancies, such as alterations in DEK, AFF2, NUTM1, IDH1-2, and SWI/SNF genes in particular, that are important from a practical standpoint for diagnosis, prognosis, and prediction of response to treatment.

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The value of GLI1 and p16 immunohistochemistry in the premolecular screening for GLI1-altered mesenchymal neoplasms

Cited by 6 publications

References 33 publications

Soft Tissue Sarcomas with Chromosomal Alterations in the 12q13-15 Region: Differential Diagnosis and Therapeutic Implications

Soft Tissue Sarcomas with Chromosomal Alterations in the 12q13-15 Region: Differential Diagnosis and Therapeutic Implications

Gastroblastoma with a novel ACTB::GLI1 gene fusion in a 19-year-old male

Molecularly defined sinonasal malignancies: an overview with focus on the current WHO classification and recently described provisional entities

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