Other epithelial tumors
2023-05-17 Paola Dal Cin, PhD , Yin (Rex) Hung, MD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.Massachussetts General Hospital,Harvard Medical School, Boston (MA)
Classification
Definition
Two recently described and molecularly defined aggressive lung neoplasms includes NUT carcinoma, characterized mainly by a t(15;19)(q15;p13) associated to BRD4::NUTM1 fusion,1-3 and thoracic SMARCA4-deficient undifferentiated tumor. 4-6
| Other epithelial tumors | Genetic marker(s) |
|---|---|
| NUT carcinoma | NUT carcinoma, previously known as NUT midline carcinoma, carries a t(15;19)(q15;p13)} associated to BRD4::NUTM1 fusion in 70% of the cases. Different NUTM1, alias NUTM1, gene partners have bee described in the remaining cases, such as BRD3, NSD3, ZNF532, or ZNF592. 2 Notably, all these non-BRD4 fusion genes interact with BRD4 as part of a complex that regulates epigenetics and transcription.2 The confirmation of NUTM1 rearrangement or chromosomal translocation t(15;19) can be made by cytogenetic analysis, in situ hybridization (FISH), RT-PCR, or next-generation sequencing, if the diagnosis is suspected despite a negative immunostaining for NUT, 3 although NUT immunohistochemistry is fairly sensitive and specific. 7 Three risk groups were defined by anatomic site and NUTM1 gene partner: best prognosis in patients with non-thoracic primary with non-BRD4 partner gene, followed by non-thoracic primary with BRD4 partner gene, and worst survival in thoracic NUT carcinoma patients, regardless of the gene partne. 8 |
| Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) | Thoracic SMARCA4-UT, previously as known as "SMARCA4-deficient thoracic sarcoma", is a high-grade malignant tumor frequently shows rhabdoid or plasmacytoid cytomorphology but generally imparts an undifferentiated appearance. Many cases of SMARCA4-UT are considered as smoking-related malignancy 4,5,9. SMARCA4-UT is characterized genetically by the presence of inactivating SMARCA4 mutations, such as nonsense or frame-shift mutations, and SMARCA4-UT frequently also harbors alterations with loss of SMARCA2. Loss of SMARCA4 encoded by SMARCA4 can be detected by immunohistochemistry. SMARCA4-UT is characterized by frequent presence of smoking-related mutational signature, high mutation burden, and frequent TP53 mutation, with a subset of tumors that can harbor other non-small cell lung carcinoma-associated mutations such as KRAS, STK11, and KEAP1. 4 The transcriptional profiles of thoracic SMARCA4-UT appear distinct from those of conventional non-small cell lung carcinomas with SMARCA4 deficiency but similar to those of malignant rhabdoid tumors.10 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 26001144 | 2015 | Primary Pulmonary NUT Midline Carcinoma: Clinical, Radiographic, and Pathologic Characterizations. | Sholl LM et al |
| 2 | 30362654 | 2018 | NUT Carcinoma: Clinicopathologic features, pathogenesis, and treatment. | French CA et al |
| 3 | 34176698 | 2021 | NUT carcinoma of the lung. | Lantuejoul S et al |
| 4 | 31751681 | 2020 | SMARCA4-Deficient Thoracic Sarcomatoid Tumors Represent Primarily Smoking-Related Undifferentiated Carcinomas Rather Than Primary Thoracic Sarcomas. | Rekhtman N et al |
| 5 | 31988001 | 2020 | Clinicopathologic Characteristics of BRG1-Deficient NSCLC. | Dagogo-Jack I et al |
| 6 | 35618627 | 2022 | Efficacy of Immune Checkpoint Inhibitors in SMARCA4-Deficient Thoracic Tumor. | Shinno Y et al |
| 7 | 19363441 | 2009 | Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. | Haack H et al |
| 8 | 32328562 | 2020 | An Anatomical Site and Genetic-Based Prognostic Model for Patients With Nuclear Protein in Testis (NUT) Midline Carcinoma: Analysis of 124 Patients. | Chau NG et al |
| 9 | 37115343 | 2023 | Thoracic SMARCA4-deficient undifferentiated tumor. | Jiang J et al |
| 10 | 26343384 | 2015 | SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas. | Le Loarer F et al |
Citation
Paola Dal Cin, PhD ; Yin (Rex) Hung, MD
Other epithelial tumors
Atlas Genet Cytogenet Oncol Haematol. 2023-05-17
Online version: http://atlasgeneticsoncology.org/solid-tumor/209154/other-epithelial-tumors
