Genetic basis of SMARCB1 protein loss in 22 sinonasal carcinomas Journal Article
| Authors: | Dogan, S.; Cotzia, P.; Ptashkin, R. N.; Nanjangud, G. J.; Xu, B.; Momeni Boroujeni, A.; Cohen, M. A.; Pfister, D. G.; Prasad, M. L.; Antonescu, C. R.; Chen, Y.; Gounder, M. M. |
| Article Title: | Genetic basis of SMARCB1 protein loss in 22 sinonasal carcinomas |
| Abstract: | SMARCB1-deficient sinonasal carcinoma (SNC) is an aggressive malignancy characterized by INI1 loss mostly owing to homozygous SMARCB1 deletion. With the exception of a few reported cases, these tumors have not been thoroughly studied by massive parallel sequencing (MPS). A retrospective cohort of 22 SMARCB1-deficient SNCs were studied by light microscopy, immunohistochemistry, fluorescence in situ hybridization (n = 9), targeted exome MPS (n = 12), and Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) (n = 10), a bioinformatics pipeline for copy number/zygosity assessment. SMARCB1-deficient SNC was found in 13 (59%) men and 9 (41%) women. Most common growth patterns were the basaloid pattern (59%), occurring mostly in men (77%), and plasmacytoid/eosinophilic/rhabdoid pattern (23%), arising mostly in women (80%). The former group was significantly younger (median age = 46 years, range = 24–54, vs 79 years, range = 66–95, p < 0.0001). Clear cell, pseudoglandular, glandular, spindle cell, and sarcomatoid features were variably present. SMARCB1-deficient SNC expressed cytokeratin (100%), p63 (72%), neuroendocrine markers (52%), CDX-2 (44%), S-100 (25%), CEA (4/4 cases), Hepatocyte (2/2 cases), and aberrant nuclear β-catenin (1/1 case). SMARCB1 showed homozygous deletion (68%), hemizygous deletion (16%), or truncating mutations associated with copy neutral loss of heterozygosity (11%). Coexisting genetic alterations were 22q loss including loss of NF2 and CHEK2 (50%), chromosome 7 gain (25%), and TP53 V157F, CDKN2A W110∗, and CTNNB1 S45F mutations. At 2 years and 5 years, the disease-specific survival and disease-free survival were 70% and 35% and 13% and 0%, respectively. SMARCB1-deficient SNCs are phenotypically and genetically diverse, and these distinctions warrant further investigation for their biological and clinical significance. © 2020 Elsevier Inc. |
| Keywords: | immunohistochemistry; adult; cancer chemotherapy; clinical article; protein expression; aged; middle aged; cancer surgery; clinical feature; cancer radiotherapy; disease free survival; antineoplastic agent; carcinoembryonic antigen; cohort analysis; retrospective study; protein p53; fluorescence in situ hybridization; immunophenotyping; sarcomatoid carcinoma; checkpoint kinase 2; heterozygosity loss; cyclin dependent kinase inhibitor 2a; gene dosage; liver cell; cytokeratin; spindle cell carcinoma; beta catenin; dna extraction; disease specific survival; chromosome 7; paranasal sinus carcinoma; antigen retrieval; homozygous deletion; high throughput sequencing; next-generation sequencing; human; male; female; article; swi/snf related matrix associated actin dependent regulator of chromatin subfamily b member 1; sinonasal smarcb1-deficient carcinoma |
| Journal Title: | Human Pathology |
| Volume: | 104 |
| ISSN: | 0046-8177 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2020-10-01 |
| Start Page: | 105 |
| End Page: | 116 |
| Language: | English |
| DOI: | 10.1016/j.humpath.2020.08.004 |
| PUBMED: | 32818509 |
| PROVIDER: | scopus |
| PMCID: | PMC7669579 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2020 -- Source: Scopus |
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