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CANCER:

Adenoid Cystic Carcinoma

1d
In summary, most ACCB have a good prognosis, but tumors with adverse histopathological features may metastasize. BCB may overlap with ACCB and TNT-NST, and their prognosis should be further studied.
Clinical • Journal
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NFIB (Nuclear Factor I B)
6d
Despite the fact that breast ACC is an indolent disease, positive margin is strongly considered a predictive factor for local recurrence and distant metastasis. Expression of ER and/or PR may be associated with aggressive behavior and distant metastasis.
Clinical
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
6d
ACC of Bartholin gland is a rare, vulvar malignancy with an aggressive and unpredictable biologic behavior. Owing to the small number of reported cases, there is no consensus regarding treatment.
KIT (KIT proto-oncogene, receptor tyrosine kinase) • TP63 (Tumor protein 63)
8d
The current evidence supports that integrated immunostaining of p63/p40 is a valuable adjunct for discerning enigmatic salivary gland tumors with true myoepithelial and/or squamous differentiation.
Review • Journal
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TP63 (Tumor protein 63)
8d
This is the largest single-institution study of PCACC in an Asian population. We described the first case of scalp PCACC with HGT, which is the only death case in our series. PCACC tends to recur locally and has metastatic potential. PCACC with HGT has a poor prognosis.
Clinical • Journal
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MYB (MYB Proto-Oncogene, Transcription Factor)
26d
ACC is an unusual type of breast carcinoma accounting for <0.1% of breast malignancies. It is characterized by a biphasic population of luminal and basaloid cells with pseudolumens filled with basement membrane material. The mean age at diagnosis is 66 years.
Clinical • Review
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HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • TP63 (Tumor protein 63) • MME (Membrane metallo-endopeptidase)
26d
The diagnosis is adenoid cystic carcinoma, solid type with basaloid features. It is characterized by solid nests composed of basaloid cells, with marked nuclear atypia, high mitotic count, and necrosis. Axillary node metastases and perineural invasion can be observed.
Clinical
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NCAM1 (Neural cell adhesion molecule 1) • TP63 (Tumor protein 63)
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TP53 expression • KIT positive
26d
Previously known as HPV-related carcinoma with adenoid cystic carcinoma-like features, this entity is a potential diagnostic pitfall with high grade adenoid cystic carcinoma. Morphologic range is wider than initially thought and not all cases display basaloid features. Although p16 is a useful screening tool, definitive diagnosis requires HPV-specific testing.
Clinical • Review
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BCL2 (B-cell CLL/lymphoma 2) • NKX2-1 (NK2 Homeobox 1) • SOX10 (SRY-Box 10) • GFAP (Glial Fibrillary Acidic Protein) • SYP (Synaptophysin)
26d
We report a lower rate of NFIB rearrangement and MYB- NFIB fusion than expected. In keeping with the other studies performed in this anatomical location, the prevalence of NFIB rearrangement and MYB-NFIB fusion seems to be lower in the vulva than elsewhere. Although MYB activation occurs in the majority of vulvar ACC, it is likely due to other mechanisms yet to be unravelled.
NFIB (Nuclear Factor I B)
|
MYB-NFIB fusion
26d
EGFR mutations in salivary gland tumours are rare, how- ever, EGFR amplification has been reported in the literature at a rate of 5- 14%. We found the EGFR amplification as 13,6% in this study. EGFR amplification is common in early-stage and female patients under 65 years of age and the mortality rate is higher in these cases.
EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR amplification
1m
Six novel gene fusions other than MYB/MYBL1-NFIB were identified. The detection of novel fusion genes and investigation of the molecular mechanism will contribute to the development of novel molecular targeted therapies for this disease.
Journal • Next-generation sequencing
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NFIB (Nuclear Factor I B)
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MYB-NFIB fusion
1m
P2, N=818, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Aug 2021 --> Aug 2022
Clinical • Trial primary completion date
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CD4 (CD4 Molecule)
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PD-L1 overexpression • PD-L1 amplification
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Opdivo (nivolumab) • Yervoy (ipilimumab)
2ms
These results explain PSGTs harbor distinct driver features of MAML2 or MYB rearrangement, accompanied with wide mutational diversity with very low rate of somatic mutation. Several important pathways, including the NOTCH and PI3K pathways, and chromatin remodeling could be targeted to improve the survival in patients with ACC.
Journal • Next-generation sequencing • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • FGFR1 (Fibroblast growth factor receptor 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ASXL1 (ASXL Transcriptional Regulator 1) • PD-1 (Programmed cell death 1) • FLT1 (Fms-related tyrosine kinase 1) • KMT2A (Lysine Methyltransferase 2A) • RBM10 (RNA Binding Motif Protein 10) • PTPRD (Protein tyrosine phosphatase receptor type D) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • FOXP1 • CCND2 (Cyclin D2) • MAML2 (Mastermind Like Transcriptional Coactivator 2) • NOTCH4 (Notch 4)
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HRAS mutation • ASXL1 mutation • FGFR1 mutation • PTPRD mutation
2ms
Furthermore, downregulation of PKD1 regulated Snail via phosphorylation at Ser-11 on Snail protein and promotion of proteasome mediated degradation, and reduced lung metastasis in vivo. Our results suggest that PKD1 induces the EMT and promotes the metastasis, which illustrate that PKD1 may be a potential prognostic biomarker and serve as a potential therapeutic target for SACC patients.
Journal
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CDH1 (Cadherin 1) • PRKD1 (Protein Kinase D1)
2ms
Multitargeted Tyrosine Kinase inhibitors such as Lenvatinib and Rivoceranib could provide disease control and limited radiographic response in unselected ACC patients...He was subsequently started on Erdafitinib, an oral selective FGFR inhibitor currently approved for FGFR positive bladder cancer... Acquired resistance mutations and other genomic abnormalities can develop in patients with ACC after treatment with Multitargeted Tyrosine Kinase inhibitors such as Lenvatinib. ctDNA is now widely available and should be included in the evaluation of patients with recurrent and metastatic ACC. FGFR genomic abnormalities can be a driver mutation in patients with refractory advanced ACC and the activity of Erdafinib should be evaluated in this subset of patients with few therapeutic options.
Clinical • Circulating tumor DNA
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BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • FGFR (Fibroblast Growth Factor Receptor)
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BRAF mutation • FGFR2 mutation • MET mutation • JAK2 V617F
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lenvatinib • AiTan (rivoceranib) • Balversa (erdafitinib)
2ms
However, this finding is sensible given that the MYB-NFIB fusion is not present in all ACC PDX models. Through our work, investigators will have a better understanding of the advantages and limitations of the utilization of the ACC PDX as a model for ACC research.
Clinical
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NFIB (Nuclear Factor I B)
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MYB-NFIB fusion
2ms
Combined chemotherapy with doxorubicin, carboplatin and cyclophosphamide was applied for two cycles but ineffective. At recent follow-ups, MRI and CT examinations revealed the diminishing perianal and pulmonary lesions. This study presented the first case of perianal ACC with multiple pulmonary metastases and particular BCOR mutations, who presented a durable response to eribulin and anlotinib, providing a potential therapeutic option for advanced refractory ACC.
Clinical • Journal
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BCL6 (B-cell CLL/lymphoma 6) • BCOR (BCL6 Corepressor) • NFIB (Nuclear Factor I B)
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BCOR mutation
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carboplatin • Focus V (anlotinib) • doxorubicin hydrochloride • Halaven (eribulin mesylate)
2ms
PTEN loss within glomeruloid pattern was associated with BCR. The presence of any cribriform pattern was associated with BCR, despite PTEN loss not significantly associated with invasive cribriform carcinoma. We speculate that other drivers independent from PTEN loss may contribute to poor prognostic features in cribriform carcinoma.
Journal
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PTEN (Phosphatase and tensin homolog) • TP63 (Tumor protein 63)
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PTEN expression
2ms
10-year OS for pure and mixed ICCs was 100% and 90%, respectively. 5-year DFS was 100% for pure ICC, and 94% for mixed ICC.
Clinical • Review • Journal
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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HER-2 positive • ER positive
2ms
Ga-FAPI-PET/CT is a promising imaging modality for ACC, increasing the accuracy of staging exams and radiotherapy planning volumes, as compared conventional to CT and MRI.
Journal
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FAP (Fibroblast activation protein, alpha)
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FAP expression
2ms
The PNI-inhibitory effect of CXCR5 knockdown or miR-187 overexpression could be reversed by elevated expression of S100A4. Conjointly, our data revealed that CXCR5 facilitated PNI through downregulating miR-187 to disinhibit S100A4 expression in SACC.
Journal
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CXCR5 (C-X-C Motif Chemokine Receptor 5) • S100A4 (S100 calcium binding protein A4)
2ms
P2, N=40, Not yet recruiting, Actuate Therapeutics Inc. | Initiation date: Jun 2021 --> Sep 2021
Clinical • Trial initiation date
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BCL2 (B-cell CLL/lymphoma 2)
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carboplatin • 9-ING-41
2ms
There are differentially expressed proteins between LACC-HGT and LACC, among which COL14A1, EML4, ITIH4, NDRG2, OGN, and RhoC may play an important role in LACC-HGT and can be used as potential targets of LACC-HGT in further study. (Chin J Ophthalmol, 2021, 57: 531-539).
Journal
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EML4 (EMAP Like 4) • CRBN (Cereblon)
2ms
Estimates for five additional subtypes were assessed. Prevalence of HER 2 positivity in SGC varies greatly based on histological subtype, with SDC, CEP, SCC, and ADC displaying the highest rates.
Retrospective data • Review
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive
3ms
A significant moderate positive correlation (r = 0.444 and p ≤ 0.001) was found between OCT4 and CD44 immunoexpression in the total sample. The high expression of OCT4 and CD44 may indicate that these proteins play an important role in identifying tumor stem cells.
Journal
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CD44 • POU5F1 (POU Class 5 Homeobox 1)
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CD44 expression • POU5F1 expression
3ms
After overexpressing S100A4, the impaired PNI ability of SACC cells induced by Twist knockdown was significantly reversed, and pseudo foot was visualized frequently. Collectively, the results indicated that CXCL12/CXCR4 might promote PNI by provoking the tumour cell to differentiate towards Schwann-like cell through Twist/S100A4 axis in SACC.
Journal
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CXCR4 (Chemokine (C-X-C motif) receptor 4) • CXCL12 (C-X-C Motif Chemokine Ligand 12) • S100A4 (S100 calcium binding protein A4)
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CXCR4 expression
3ms
Finally, as anticipated, gene fusions were not detected in any of the five acinic cell carcinomas included in the cohort. In summary, targeted RNA sequencing represents a diagnostically useful ancillary technique for identifying a variety of existing, and novel, fusion transcripts in the classification of salivary gland neoplasms.
Clinical • Journal
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NFIB (Nuclear Factor I B) • CRTC1 (CREB Regulated Transcription Coactivator 1) • MAML2 (Mastermind Like Transcriptional Coactivator 2) • HMGA2 (High mobility group AT-hook 2)
4ms
While the trial did not meet its prespecified response endpoint, ATRA alone or in combination may be a low toxicity treatment for disease growth stabilization in R/M ACC.
P2 data • Journal
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NOTCH1 (Notch 1) • MYB (MYB Proto-Oncogene, Transcription Factor)
4ms
Comparing gene expression among SGTs types, we observed higher expression of SMAD4 in ACCs, as well as higher expression of ITGB6 and decreased expression of SMAD2 in MECs. Conclusion Altered expression of genes associated with TGF-β signaling may be involved in tumor progression and this knowledge is useful for the application of novel biological markers.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SMAD4 (SMAD family member 4) • TGFB1 (Transforming Growth Factor Beta 1) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • SMAD2 (SMAD Family Member 2)
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MYC expression
4ms
Comparing gene expression among SGTs types, we observed higher expression of SMAD4 in ACCs, as well as higher expression of ITGB6 and decreased expression of SMAD2 in MECs. Conclusion Altered expression of genes associated with TGF-β signaling may be involved in tumor progression and this knowledge is useful for the application of novel biological markers.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SMAD4 (SMAD family member 4) • TGFB1 (Transforming Growth Factor Beta 1) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • SMAD2 (SMAD Family Member 2)
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MYC expression
4ms
Comparing gene expression among SGTs types, we observed higher expression of SMAD4 in ACCs, as well as higher expression of ITGB6 and decreased expression of SMAD2 in MECs. Conclusion Altered expression of genes associated with TGF-β signaling may be involved in tumor progression and this knowledge is useful for the application of novel biological markers.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SMAD4 (SMAD family member 4) • TGFB1 (Transforming Growth Factor Beta 1) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • SMAD2 (SMAD Family Member 2)
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MYC expression
4ms
Comparing gene expression among SGTs types, we observed higher expression of SMAD4 in ACCs, as well as higher expression of ITGB6 and decreased expression of SMAD2 in MECs. Conclusion Altered expression of genes associated with TGF-β signaling may be involved in tumor progression and this knowledge is useful for the application of novel biological markers.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SMAD4 (SMAD family member 4) • TGFB1 (Transforming Growth Factor Beta 1) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • SMAD2 (SMAD Family Member 2)
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MYC expression
4ms
Loss or overexpression of SWI/SNF results in tumor progression and chemoresistance dependent on tumor tissue origin and type: primary or metastatic. Financial support: Polpharma Scientific Foundation 5/XVII/18 (TJS)
SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1
4ms
Conclusion Our results indicate that SWI/SNF dependent chromatin remodeling and mRNA splicing are not separate process and their parallel aberration is one of the major causes of alterations in salivary gland ACC. Additionally, such disability of chromatin related processes and abnormal splicing may be directly related with m6 N RNA methylation processes.
SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • METTL3 (Methyltransferase Like 3)
4ms
Conclusion Our results indicate that SWI/SNF dependent chromatin remodeling and mRNA splicing are not separate process and their parallel aberration is one of the major causes of alterations in salivary gland ACC. Additionally, such disability of chromatin related processes and abnormal splicing may be directly related with m6 N RNA methylation processes.
SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • METTL3 (Methyltransferase Like 3)
4ms
Conclusion Our results indicate that SWI/SNF dependent chromatin remodeling and mRNA splicing are not separate process and their parallel aberration is one of the major causes of alterations in salivary gland ACC. Additionally, such disability of chromatin related processes and abnormal splicing may be directly related with m6 N RNA methylation processes.
SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • METTL3 (Methyltransferase Like 3)
4ms
Loss or overexpression of SWI/SNF results in tumor progression and chemoresistance dependent on tumor tissue origin and type: primary or metastatic. Financial support: Polpharma Scientific Foundation 5/XVII/18 (TJS)
SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1
4ms
Loss or overexpression of SWI/SNF results in tumor progression and chemoresistance dependent on tumor tissue origin and type: primary or metastatic. Financial support: Polpharma Scientific Foundation 5/XVII/18 (TJS)
SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1
4ms
Conclusion Our results indicate that SWI/SNF dependent chromatin remodeling and mRNA splicing are not separate process and their parallel aberration is one of the major causes of alterations in salivary gland ACC. Additionally, such disability of chromatin related processes and abnormal splicing may be directly related with m6 N RNA methylation processes.
SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • METTL3 (Methyltransferase Like 3)
4ms
Loss or overexpression of SWI/SNF results in tumor progression and chemoresistance dependent on tumor tissue origin and type: primary or metastatic. Financial support: Polpharma Scientific Foundation 5/XVII/18 (TJS)
SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1
4ms
HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.
Clinical • Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 amplification • HER-2 overexpression
4ms
The GATA6 gene may be related to the occurrence and progression of certain oral cancers.
Preclinical • Journal
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GATA6 (GATA Binding Protein 6)
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GATA6 expression
4ms
Our results showed that C3(1)-TAg animals with C57BL/6 J background develop solid-basaloid adenoid cystic carcinomas with increased fibrosis, decreased area of adipocytes, and a high proliferative index, which are triple-negative for progesterone, estrogen, and human epidermal growth factor receptor 2 (HER2) receptors. Our results also revealed that tumor development is slower in the C57BL/6 J background when compared with the FVB strain, providing a better model to study the different stages in breast cancer progression.
Journal
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HER-2 (Human epidermal growth factor receptor 2)
4ms
HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.
Clinical • Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 amplification • HER-2 overexpression
4ms
The SD-LDVxN flap is a highly resourceful solution to reconstruct complex parotid defects, especially those that sacrifice the facial nerve. The vascularized nerve graft allows for primary facial reanimation. Nerve recovery may be superior to what could be expected with a conventional nerve graft.
Clinical • Journal
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ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
4ms
Furthermore, patients with this subtype of prostate cancer need appropriately designed, and maybe a totally different follow-up regimen as PSA is of no use for BCCP patients. Finally, diagnosis of BCCIS, if agreed upon its existence needs to be studied in larger cohorts as a precursor lesion.
Clinical • Journal
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NCOA4 (Nuclear Receptor Coactivator 4)
5ms
Finally, we identified tau tubulin kinase 2 (TTBK2) as being possibly involved in the production of PC in SGTs. Taken together, our findings indicate that SGTs that exhibit basaloid/myoepithelial differentiation (PA, BCA, AdCC, and BCAc) are ciliated, and their PC exhibit tumour-specific characteristics, are involved in activation of the hedgehog pathway, and are associated with TTBK2 upregulation, providing a significant and important link between SGT tumourigenesis and PC.
Journal
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GLI1 (GLI Family Zinc Finger 1)
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GLI1 expression
5ms
ACC is a genetically heterogenous disease with an immune-excluded microenvironment . NOTCH1 mutations were associated with worse, while MYB:NFIB fusion was not associated with prognosis . Our study shows that M2 macrophages and MYC are potential novel therapeutic targets in ACC.
TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NOTCH1 (Notch 1) • ARID1A (AT-rich interaction domain 1A) • KMT2C (Lysine Methyltransferase 2C) • KDM6A (Lysine Demethylase 6A) • MYB (MYB Proto-Oncogene, Transcription Factor) • NFIB (Nuclear Factor I B) • EGF (Epidermal growth factor)
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NOTCH1 mutation • MYC expression • MYB-NFIB fusion • NOTCH1 expression
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MI Tumor Seek™
5ms
Multitargeted Tyrosine Kinase inhibitors (TKIs) as Lenvatinib and Rivoceranib can provide disease control and limited radiographic response in unselected ACC patients...The patient was started on Erdafitinib, an oral selective FGFR inhibitor, achieving a partial response at the primary site and metastatic liver lesions and remained on therapy for 7 months... Patients treated with lenvantinib or other TKIs may develop acquired resistance mutations and other genomic abnormalities . ctDNA can reveal additional therapeutic targets not present on tNGS and can be repeated serially . FGFR genomic abnormalities can be a driver mutation in patients with refractory advanced ACC and the activity of Erdafinib should be evaluated in this subset of patients with few therapeutic options.
Clinical • Circulating tumor DNA
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BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • FGFR (Fibroblast Growth Factor Receptor)
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KRAS mutation • BRAF mutation • FGFR1 amplification • FGFR2 mutation • NOTCH1 mutation • JAK2 mutation • BRAF amplification
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lenvatinib • AiTan (rivoceranib) • Balversa (erdafitinib)
5ms
KD033 has been well tolerated early in dose escalation with on-mechanism pharmacodynamics consistent with IL-15 agonism.
P1 data
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • IL2 (Interleukin 2)
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KD033
5ms
The lack of pan-TRK immunoreactivity in a subset of SCs is suggestive of atypical exons 4 to 14 or exons 5 to 14 ETV6-NTRK3 fusion or non-NTRK alternative fusion partners such as ETV6-RET. Pan-TRK staining can serve as a strong diagnostic marker to distinguish SC from it mimics and to select patients eligible for TRK inhibitor clinical trials.
Journal
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RET (Ret Proto-Oncogene) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK3 fusion • RET fusion • ETV6-NTRK3 fusion
5ms
This is the first study to demonstrate that several types of SGC express Trop-2 with variable intensity. Since there are currently few systemic treatment options for advanced SGCs, Trop-2 represents a promising target for further clinical studies, for instance, with sacituzumab govitecan.
Journal
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TROP2 (Trophoblast Cell Surface Antigen 2)
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Trodelvy (sacituzumab govitecan-hziy)
5ms
Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.
Journal • Next-generation sequencing
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RET (Ret Proto-Oncogene) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NFIB (Nuclear Factor I B) • NR4A3 (Nuclear receptor subfamily 4 group A member 3) • NTRK (Neurotrophic receptor tyrosine kinase) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • ZBTB7A (Zinc finger and BTB domain containing 7A) • MAML2 (Mastermind Like Transcriptional Coactivator 2)
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NTRK2 fusion • RET fusion • MYB-NFIB fusion
5ms
This study confirms the expression of SSTR2 in glandular salivary carcinomas and an inverse correlation in expression levels between SSTR2 and Ki-67. This lays a foundation for novel treatment options in salivary metastatic cancers where SSTR2 may be a potential novel therapeutic target.
Retrospective data • Journal
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SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2)
5ms
In this study, these identified DEGs were considered to have a potential influence on AdCC but have not been studied in this disease. The analysis results promote our understanding of the molecular mechanisms and biological processes of AdCC, which might be useful for targeted therapy or diagnosis.
Journal
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SOX2 • TGFB1 (Transforming Growth Factor Beta 1) • ITGA9 (Integrin Subunit Alpha 9) • MIR132 (MicroRNA 132)
5ms
Also, FASN expression was significantly higher in high-grade AdCC and MEC when compared to low-grade tumors (p < 0.05). We concluded that FASN expression was correlated to tumor aggressiveness and cellular differentiation in salivary gland carcinomas.
Journal
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FAS (Fas cell surface death receptor) • FASN (Fatty acid synthase)
6ms
When the density of mast cells, myofibroblasts and the expression of PAR-2 protein, IL-6, and TGFβ1 were compared, it was no statistically significant difference between tumors with and without myoepithelial differentiation. The results of present study suggest a possible participation of mast cells and especially of PAR-2 in the development and progression of malignant salivary cancers, regardless of myoepithelial content.
Journal
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IL6 (Interleukin 6) • TGFB1 (Transforming Growth Factor Beta 1)
6ms
Thus, tumors developed from the intraoral minor salivary glands, with solid pattern, perineural invasion, locally aggressive and with lymph node metastasis were the most reactive. Therefore, these transcription factors could be useful as prognostic biomarkers and efficient therapeutic targets in such salivary malignancies.
Journal
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ZEB1 (Zinc Finger E-box Binding Homeobox 1)
6ms
Clinical • New P2 trial
|
BCL2 (B-cell CLL/lymphoma 2)
|
carboplatin • 9-ING-41
6ms
In this study, we displayed the morphologically and genetic featured PDXs which recapitulated the heterogeneity of original ACC tumors, indicating that the models could be used as a platform for drug screening for therapy response. The feasibility of combination treatment approaches for dual targets were confirmed, providing new regimens for personalized therapies in ACC.
Preclinical • Journal • Combination therapy
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NOTCH1 (Notch 1) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NOTCH2 (Notch 2) • KDM6A (Lysine Demethylase 6A) • MYB (MYB Proto-Oncogene, Transcription Factor) • NFIB (Nuclear Factor I B)
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PIK3CA mutation • PIK3CA amplification • MYB-NFIB fusion
6ms
the final diagnosis can only be assessed based on the results of the histopathological and immunohistochemical examination. Breast-conserving surgery may be an alternative treatment strategy, and axillary lymph node dissection or sentinel node biopsy may not be necessary in some cases.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HR positive • HR negative
6ms
The patient received chemotherapy with TRK inhibitor larotrectinib and carboplatin, which caused shrinkage of metastatic lung nodules. This is the first report of cervical BSCC with extensive molecular workup, which detected multiple genetic events, including targetable ones, which are potentially implicated in the development of a tumor. The accumulation of data and further studies on this tumor are necessary to define its diagnostic criteria and its clinical and biological behavior.
Clinical • Journal
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PALB2 (Partner and localizer of BRCA2) • KMT2D (Lysine Methyltransferase 2D) • JAK1 (Janus Kinase 1) • POLD1 (DNA Polymerase Delta 1) • NOTCH2 (Notch 2) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • AMER1 (APC Membrane Recruitment Protein 1) • DAXX (Death-domain associated protein)
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PIK3CA mutation • NTRK2 fusion • KMT2D mutation • POLD1 mutation
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Vitrakvi (larotrectinib) • carboplatin
6ms
There was no association between TIL expression and survival. These data suggest that PD-L1 and TIL expression are unlikely to be useful as predictive biomarkers for response to immunotherapy.
Journal • Tumor-Infiltrating Lymphocyte • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8)
|
PD-L1 expression • PD-L1 negative
6ms
Awareness of these tumors and knowledge of available ancillary studies to confirm the diagnosis is important to avoid misdiagnosis which might lead to differences in treatment, management, and prognosis. Further studies are needed to identify biomarkers to better predict patient's outcome and for individual management and treatment of patients.
Journal
|
EWSR1 (EWS RNA Binding Protein 1)
6ms
Further, chemotherapy (carboplatin/paclitaxel) was conducted on the PDX model. All three PDX models had histopathological features similar to those of the original tumors, and retained the MYB-NFIB fusion gene. We successfully established PDX models of adenoid cystic carcinoma, including an HGT model, which was characterized by detailed clinical and genomic information. Tumors that show HGT characteristics may be drug-sensitive, and can be used in the development of personalized cancer treatments.
Clinical
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • NFIB (Nuclear Factor I B) • SOX10 (SRY-Box 10) • TP63 (Tumor protein 63)
|
MYB-NFIB fusion
|
carboplatin • paclitaxel
7ms
Collectively, these findings provide a strong molecular rationale for exploring PRT543 as a potential therapeutic option for ACC tumors. PRT543 is currently under evaluation in a Phase I clinical trial in patients with advanced solid tumors and hematological malignancies (NCT03886831).
NOTCH1 (Notch 1) • MYB (MYB Proto-Oncogene, Transcription Factor) • NFIB (Nuclear Factor I B) • PRMT5 (Protein Arginine Methyltransferase 5) • FOXM1 (Forkhead Box M1) • GATA3 (GATA binding protein 3) • SOX4 (SRY-Box Transcription Factor 4)
|
NOTCH1 mutation • MYB-NFIB fusion • NOTCH1 expression
|
PRT543
7ms
Our study revealed strong nuclear staining for MYB in all ACC cases and in none of other TNBC cases, indicating that strong MYB staining by immunohistochemistry is a sensitive and specific marker for diagnosis of Adenoid cystic carcinoma of breast. Thus, we recommend routine staining for MYB antibody in all TNBCs with a solid/ basaloid morphology, to diagnose cases of ACC.
HER-2 (Human epidermal growth factor receptor 2) • MYB (MYB Proto-Oncogene, Transcription Factor) • NFIB (Nuclear Factor I B)
|
HER-2 negative
7ms
Almost all PAs show strong expression of GFAP. In contrast, most malignant neoplasms that can mimic PA on small biopsies show only rare expression. Other benign tumours composed of abluminal cells also show strong expression of GFAP highlighting the spectrum these tumours share with PA.
GFAP (Glial Fibrillary Acidic Protein)
7ms
NR4A3 FISH has a sensitivity of 58% and specificity of 100% in detecting ACC which suggests that NR4A3 rearrangement-driven upregulation is a recurrent, specific oncogenic event in ACC, consistent with prior results. 100% concordance between matched resections/FNAs validates its potential utility on cytology samples. FISH (+) ACC had no specific morphologic correlates.
NR4A3 (Nuclear receptor subfamily 4 group A member 3)
7ms
Our data suggest that MYB expression by RNA ISH is sensitive and specific for AdCC, with an overall sensitivity of 87% and specificity of 91%. MYB RNA ISH assay can be applied in assisting the diagnosis of AdCC on cytology FNA samples. The significance of lower sensitivity in AdCCs from trachea and lung is uncertain, requiring future large series of studies to validate or explore further of our findings
MYB (MYB Proto-Oncogene, Transcription Factor) • NFIB (Nuclear Factor I B)
|
MYB-NFIB fusion
7ms
In conclusion, FOXC1 was a highly specific marker for TNBC. In TNBC, FOXC1 expression was positively correlated with basal markers, and negatively correlated with apocrine-related markers, which suggested that immunohistochemical detection of FOXC1 expression can be used as an additional diagnostic tool for prediction of triple-negative phenotype and further classification in TNBC.
HER-2 (Human epidermal growth factor receptor 2) • FOXC1 (Forkhead Box C1)
|
FOXC1 expression
7ms
Overexpression of HIF-1ɑ protein was significantly associated with reduced disease free survival. Solid histologic pattern and bone erosion were the most important predictors of poor outcome. HIF-1ɑ as a potential novel therapeutic target in the management of aggressive lacrimal gland ACC needs to be explored.
HIF1A (Hypoxia inducible factor 1, alpha subunit)
|
HIF1A expression
7ms
NOR-1 immunohistochemical staining can be reliably performed on cytologic smears and liquid-based preparations of salivary gland tumors. This provides a valuable tool for distinguishing ACC-SG from its cytologic mimics on preoperative cytology with excellent sensitivity and specificity to optimize patient management.
NR4A3 (Nuclear receptor subfamily 4 group A member 3)
10ms
P1, N=54, Recruiting, VM Oncology, LLC | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Jun 2021 --> Jun 2022
Clinical • Trial completion date • Trial primary completion date
|
NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
|
NTRK1 fusion • NTRK1 mutation • NTRK expression
|
VMD-928
12ms
P1/2, N=165, Recruiting, Cellestia Biotech AG | Trial completion date: Jun 2021 --> Dec 2021 | Trial primary completion date: Jun 2021 --> Dec 2021
Clinical • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
CB-103
over1year
P1, N=54, Recruiting, VM Oncology, LLC | Trial completion date: May 2020 --> Dec 2021 | Trial primary completion date: Nov 2019 --> Jun 2021
Clinical • Trial completion date • Trial primary completion date
|
NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
|
NTRK1 fusion • NTRK1 mutation • NTRK expression
|
VMD-928
over7years
P2, N=67, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed
Clinical • Trial completion
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression • EGFR expression
|
lapatinib