scholarly journals Genetic analysis of sinonasal undifferentiated carcinoma discovers recurrent SWI/SNF alterations and a novel PGAP3-SRPK1 fusion gene

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Molly E. Heft Neal ◽  
Andrew C. Birkeland ◽  
Apurva D. Bhangale ◽  
Jingyi Zhai ◽  
Aditi Kulkarni ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Cell Line ◽  
Gene Fusion ◽  
Fusion Gene ◽  
Undifferentiated Carcinoma ◽  
Driver Mutations ◽  
Cancer Center ◽  
Skull Base Tumor ◽  
Sinonasal Undifferentiated Carcinoma ◽  
Significant Difference

Abstract Background Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown. Methods We evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We performed exome sequencing to characterize a series of SNUC tumors (n = 5) and cell line (MDA8788–6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion. Results Overall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/− CRT and CRT alone. Tobacco use was the only significant predictor of survival. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. We also validated a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. Conclusion Collectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.

scholarly journals Genetic Analysis of Sinonasal Undifferentiated Carcinoma Discovers Recurrent SWI/SNF Alterations and a novel PGAP3-SRPK1 Fusion Gene

2020 ◽  
Author(s):  
Molly Heft Neal ◽  
Andrew Birkeland ◽  
Apurva Bhangale ◽  
Jingyi Zhai ◽  
Aditi Kulkarni ◽  
...  
Keyword(s):  
Cell Line ◽  
Gene Fusion ◽  
Fusion Gene ◽  
Gene Families ◽  
Undifferentiated Carcinoma ◽  
Driver Mutations ◽  
Cancer Center ◽  
Skull Base Tumor ◽  
Wild Type ◽  
Sinonasal Undifferentiated Carcinoma

Abstract Background: Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown.Methods: We evaluate survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We perform exome sequencing to characterize a series of SMARCB1 wild type tumors and cell line including identification of high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA was utilized for validation of a novel PGAP3-SRPK1 gene fusion. Results: We discover recurrent aberrations to the SWI/SNF and FAT gene families. We also validate a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. Conclusion: Collectively, these data demonstrate recurrent alterations in the SWI/SNF and FAT gene families and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.

scholarly journals Induction Chemotherapy Response as a Guide for Treatment Optimization in Sinonasal Undifferentiated Carcinoma

2019 ◽  
Vol 37 (6) ◽  
pp. 504-512 ◽  
Author(s):  
Moran Amit ◽  
Ahmed S. Abdelmeguid ◽  
Teemaranawich Watcherporn ◽  
Hideaki Takahashi ◽  
Samantha Tam ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Postoperative Radiotherapy ◽  
Disease Free Survival ◽  
Undifferentiated Carcinoma ◽  
Locoregional Therapy ◽  
Cancer Center ◽  
Chemotherapy Response ◽  
Sinonasal Undifferentiated Carcinoma ◽  
Definitive Therapy ◽  
Definitive Surgery

PURPOSE Multimodal therapy is a well-established approach for the treatment of sinonasal undifferentiated carcinoma (SNUC); however, the optimal sequence of the various treatments modalities is yet to be determined. This study aimed to assess the role of induction chemotherapy (IC) in guiding definitive therapy in patients with SNUC. METHODS Ninety-five previously untreated patients diagnosed with SNUC and treated between 2001 and 2018 at The University of Texas MD Anderson Cancer Center were included in the analysis. Patients were treated with curative intent and received IC before definitive locoregional therapy. The primary end point was disease-specific survival (DSS). Secondary end points included overall and disease-free survival, disease recurrence, and organ preservation. RESULTS A total of 95 treatment-naïve patients were included in the analysis. For the entire cohort, the 5-years DSS probability was 59% (95% CI, 53% to 66%). In patients who had partial or complete response to IC, the 5-year DSS probabilities were 81% (95% CI, 69% to 88%) after treatment with definitive concurrent chemoradiotherapy (CRT) after IC and 54% (95% CI, 44% to 61%) after definitive surgery and postoperative radiotherapy or CRT after IC (log-rank P = .001). In patients who did not experience at least a partial response to IC, the 5-year DSS probabilities were 0% (95% CI, 0% to 4%) in patients who were treated with concurrent CRT after IC and 39% (95% CI, 30% to 46%) in patients who were treated with surgery plus radiotherapy or CRT (adjusted hazard ratio of 5.68 [95% CI, 2.89 to 9.36]). CONCLUSION In patients who achieve a favorable response to IC, definitive CRT results in improved survival compared with those who undergo definitive surgery. In patients who do not achieve a favorable response to IC, surgery when feasible seems to provide a better chance of disease control and improved survival.

Geographic variation of extranodal sites of mucosal associated lymphoid tissue lymphoma (MALToma): Analysis of series from two institutions.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18534-e18534
Author(s):  
Kalid Adab ◽  
Daniel Oscar Persky ◽  
Jose Guillen-Rodriguez ◽  
Lisa M. Rimsza ◽  
Yvette M. Frutiger ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Cook County ◽  
Cancer Center ◽  
Cook County Hospital ◽  
Skull Base Tumor ◽  
Skin Involvement ◽  
Significant Difference ◽  
Frequent Site ◽  
The Difference ◽  
The University

e18534 Background: MALToma represents about 5% of Non-Hodgkin lymphomas (NHL). Prior studies report stomach to be the most common site of involvement (35-50%), while skin (16%) or salivary glands (26%) were reported to be the 2nd most frequent site in 2 different studies. Geographical variation may affect the proportions of primary sites of MALToma, which could provide further clues to investigating their causes. Methods: The data was obtained on 91 consecutive patients from the University of Arizona Cancer Center (UACC) clinical and pathological databases, and 25 patients from the Cook County Hospital (CCH) database, seen between 2005 and 2011.The frequency of clinical characteristics and their relation to survival were analyzed and compared between UACC and CCH. Results: UACC and CCH cohorts were balanced for gender (M:F ratio 0.65) and age (median 63 y (range, 26-88), but not for race or/and ethnicity. While at CCH 36% of pts were African-American (AA), 28% Hispanic (any race), 12% Caucasian and 20% unknown; at UACC 88% of pts were Caucasian, 10% Hispanic and 1% AA (p<0.0001). UACC had 8% pts with > 1 extranodal site, while CCH had none. The primary sites of MALToma were also different. At CCH, similarly to what’s commonly reported in the literature, 40% of pts had primary gastric involvement, 20% salivary gland, 12% lung, 8% orbit, 8% thyroid, 4% intestine, 4% skull base tumor, and 4% breast. At UACC, however, 22% of pts had primary skin involvement, 19% gastric, 16% lung, 13% orbit, 8% salivary gland, 6% intestine, 5% breast, 3% thyroid and 8% other. The difference was statistically significant for the frequency of primary skin (p=0.006) but not gastric involvement (p=0.084). 80% of patients with primary skin involvement were Caucasian. The median follow-up of the survivors was 18 months for both groups, with no statistically significant difference in median progression-free (7.5 years) or overall survival (14.6 years). Conclusions: There was higher prevalence of Caucasian race and skin involvement at UACC than at CCH. We speculate that sun-induced photodamage causes chronic inflammation contributing to eventual malignant transformation to primary skin MALToma.

Incidence and Survival Patterns of Sinonasal Undifferentiated Carcinoma in the United States

2014 ◽  
Vol 75 (S 01) ◽  
Author(s):  
Kyle Chambers ◽  
Ashton Lehmann ◽  
Aaron Remenschneider ◽  
Matthew Dedmon ◽  
Bharat Yarlagadda ◽  
...  
Keyword(s):  
United States ◽  
The United States ◽  
Undifferentiated Carcinoma ◽  
Sinonasal Undifferentiated Carcinoma ◽  
Survival Patterns

Multidisciplinary Management of Sinonasal Undifferentiated Carcinoma

Skull Base ◽  
2007 ◽  
Vol 17 (S 2) ◽  
Author(s):  
Vu Ho ◽  
Daniel Ward ◽  
Erin Lin ◽  
Jason Heth ◽  
Janet Urban ◽  
...  
Keyword(s):  
Undifferentiated Carcinoma ◽  
Multidisciplinary Management ◽  
Sinonasal Undifferentiated Carcinoma

Five-year Survival Analysis of a Cohort of Hepatocellular Carcinoma Patients Who Treated at the National Cancer Center, Korea

2007 ◽  
Vol 13 (4) ◽  
pp. 530 ◽  
Author(s):  
Kyung Woo Park ◽  
Joong-Won Park ◽  
Tae Hyun Kim ◽  
Jun Il Choi ◽  
Seong Hoon Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Cancer Center

scholarly journals PATH-19. MOLECULAR, HISTOLOGIC AND CLINICAL CHARACTERISTICS OF OLIGODENDROGLIOMAS: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii168
Author(s):  
Antonio Dono ◽  
Kristin Alfaro-Munoz ◽  
Yuanqing Yan ◽  
Carlos Lopez-Garcia ◽  
Zaid Soomro ◽  
...  
Keyword(s):  
Health Science ◽  
Cancer Center ◽  
Subtotal Resection ◽  
Adjuvant Radiation ◽  
Science Center ◽  
Who Grade ◽  
Pik3ca Mutations ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.

Targeting MET Amplification with Crizotinib in a Case of Sinonasal Undifferentiated Carcinoma

2021 ◽  
Vol 39 (3) ◽  
pp. 235-239
Author(s):  
Hannah Robinson ◽  
Michelle Green ◽  
Gauri Radkar ◽  
Neal Ready ◽  
John Strickler
Keyword(s):  
Undifferentiated Carcinoma ◽  
Sinonasal Undifferentiated Carcinoma ◽  
Met Amplification

scholarly journals FOXO1 gene involvement in a non-rhabdomyosarcomatous neoplasm

2021 ◽  
Author(s):  
Simon Haefliger ◽  
Muriel Genevay ◽  
Michel Bihl ◽  
Romina Marone ◽  
Daniel Baumhoer ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Soft Tissue ◽  
Genetic Heterogeneity ◽  
Gene Fusion ◽  
Fusion Gene ◽  
Soft Tissue Tumors ◽  
Gene Fusions ◽  
Mesenchymal Tumors ◽  
Myoepithelial Differentiation ◽  
Foxo1 Gene

AbstractMyoepithelial neoplasms of soft tissue are rare tumors with clinical, morphological, immunohistochemical, and genetic heterogeneity. The morphological spectrum of these tumors is broad, and the diagnosis often requires immunostaining to confirm myoepithelial differentiation. Rarely, tumors show a morphology that is typical for myoepithelial neoplasms, while the immunophenotype fails to confirm myoepithelial differentiation. For such lesions, the term “myoepithelioma-like” tumor was introduced. Recently, two cases of myoepithelioma-like tumors of the hands and one case of the foot were described with previously never reported OGT-FOXO gene fusions. Here, we report a 50-year-old woman, with a myoepithelial-like tumor localized in the soft tissue of the forearm and carrying a OGT-FOXO1 fusion gene. Our findings extend the spectrum of mesenchymal tumors involving members of the FOXO family of transcription factors and point to the existence of a family of soft tissue tumors that carry the gene fusion of the OGT-FOXO family.

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