Although there is an immunophenotypic overlap with PH, ES typically lacks reactivity to CD31, FLI1, and SMARCB1
(INI-1), unlike PH.
Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with "neuroblastoma-like" schwannomatosis and a novel germline SMARCB1
Indeed, loss of SMARCB1
, a subunit of the complex, is the unique genetic alteration which drives rhabdoid tumors and is associated with blocking of the differentiation, reprogramming towards an oncogenic transcriptional program and activation of tumorigenic signaling [93-95].
In our case, the only detected genomic alteration was SMARCB1
(SWItch/sucrose nonfermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1).
The immunohistochemical analysis revealed a loss of SMARCB1
protein expression and pathological examination of the placenta showed an invasion of both fetal and maternal compartments (Figure 5).
Genes Tested AtP ALK APC ATM BAP1 BRCA2 BRIP1 BUB1B CDC73 CDH1 CEP57 CHEK2 CYLD DDB2 DICER1 ERCC3 ERCC4 ERCC5 EXT1 EXT2 FANCD2 FANCE FANCF FANCG FANCI GATA2 GPC3 HNF1A HOXB13 HRAS MLH1 MHS2 MSH6 MUTYH NBN PHOX2B PMS1 PMS2 PPM1D PRF1 RAD51D RBI RECQL4 RET RHBDF2 SDHC SDHD SLX4 SMAD4 SMARCA4 TP53 TSC1 TSC2 VHL WT1 BARD1 BLM BMPR1A BRCA1 CDK4 CDKN1C CDKN2A CEBPA DI53L2 EGFR EPCAM ERCC2 EZH2 FANCA FANCB FANCC FANCL FANCM FH FLCN KIT MAX MEN1 MET NF1 NF2 NSD1 PALB2 PRKAR1A PTCH1 PTEN RAD51C RUN XI SBDS SDHAF2 SDHB SMARCB1
STK11 5UFU TMEM127 WRN XPA XPC This chart shows all 98 cancer susceptible genes included in this new test.
Following delineation of the roles of SMARCB1
(INI1) in different neoplasms , SMARCA4 (BRG1) on chromosome 19p13.2 has been recently increasingly recognized as the main or sole molecular driver event in SMARCB1-intact rhabdoid malignancies including in particular the vast majority of small cell carcinomas of ovary, hypercalcemic type (SCCOHT) .
Mutations in other components of SWI/SNF chromatin remodeling complex such as SMARCC2, SMARCC1, SMARCB1
, SMARCA4, and SMARCA2 have also been commonly reported in HCCs.
En cuanto a mutaciones especificas se ha asociado al tumor teratoideo/rabdoide atipico el gen SMARCB1
, y alteraciones genomicas del BRAF, en especial la fusion del KIAA1549 y BRAF (22), y la activacion de la via ERK/MAPK; tambien se ha observado asociacion a mutaciones en histona H3.3 y mutaciones en el gen TP5325, aunque en menor frecuencia (23).
The common genetic basis for rhabdoid tumours is a deletion and/or mutation of the INI1 gene on chromosome 22 (22q11), inactivating the tumour suppressor gene SMARCB1
, though these tumours can lack this mutation as seen in this case.[sup.1]
(60) The diagnosis of HPV-related multiphenotypic sinonasal carcinoma requires HPV-specific testing as part of the tumor definition (Figure 4, B), (61) whereas for the diagnosis of SMARCB1
(INI1)-deficient carcinoma, loss of nuclear immunohistochemical staining for INI1 is required.
Balanced translocations disrupting SMARCB1
are hallmark recurrent genetic alterations in renal medullary carcinomas.