Loss of BRM expression is a frequently observed event in poorly differentiated clear cell renal cell carcinoma

Abstract

We have shown that loss of BRM expression is a common feature among poorly differentiated tumours in clear cell RCCs. We hypothesize that loss of BRM expression is involved in tumor de-differentiation in clear cell RCCs and may play an important role during tumour progression.

Frequent co‐inactivation of the SWI/SNF subunits SMARCB1, SMARCA2 and PBRM1 in malignant rhabdoid tumours

“…Moreover, SMARCA2 has been found to be inactivated in 10–20% of multiple solid tumour types, including lung, breast, colon, oesophageal, ovarian, bladder, prostate, gastric and head/neck tumours . In our recent study, loss of SMARCA2 expression was frequently observed in poorly differentiated clear cell RCCs . However, it has been suggested that the subunits of the SWI/SNF complex can compensate for each other and ameliorate the impact of inactivation of one of these subunits .…”

“…In mammals, the SWI/SNF complex is a polymorphic assembly of at least 13 subunits encoded by 26 genes, mainly including SMARCB1, SMARCA4 (BRG1), SMARCA2 (BRM), ARID1A (BAF250A), and PBRM1 (BAF180), which are critical for growth and cancer development . Frequent inactivation of these genes has been reported in various tumours, including renal, bladder, prostate, ovarian, endometrioid, hepatocellular, gastric, breast, lung, pancreatic, colon and soft tissue malignancy in recent studies . Although SMARCB1 has been extensively reported in the pathogenesis of MRTs, recent studies also suggest that inactivation or absence of one subunit could be compensated for by other subunits of the SWI/SNF complex, which implies the potential involvement of other subunits in MRTs.…”

The multi-omic landscape of transcription factor inactivation in cancer

“…For instance, between lung, kidney, bladder and colon tissue, ten TFs ( CASZ1 , NR3C2 , THRA , SETBP1 , SMARCA2 , MEIS2 , NFIC , PURA , KLF13 , TCF21 ) were commonly overexpressed in all these tissues compared with hESCs and also commonly silenced in LSCC, LUAD, KIRC, KIRP, BLCA and COAD compared with their respective normal tissues. This list includes known tumour suppressors such as the nuclear receptor NR3C2 [69], the helix-loop-helix transcription factor TCF21 [70], and SMARCA2 (also known as BRM ), a member of the SNF/SWI chromatin remodelling complex [71–73]. Interestingly, however, the list also includes SETBP1 , a TF which has been reported to be oncogenic in myeloid neoplasms [74, 75], highlighting the need to explore a potential tumour suppressive role of this TF in the context of epithelial cancer.…”

Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects

“…However, loss of nuclear expression of INI1 is commonly observed in rhabdoid cells of renal medullary carcinoma [6,17,29]. It has been suggested that loss of Brahma (BRM) expression may be involved in the dedifferentiation of clear cell RCC exhibiting anaplastic or rhabdoid morphology [30].…”