PMID- 30980040
OWN - NLM
STAT- MEDLINE
DCOM- 20200706
LR  - 20231104
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 32
IP  - 9
DP  - 2019 Sep
TI  - Distinctive mechanisms underlie the loss of SMARCB1 protein expression in renal 
      medullary carcinoma: morphologic and molecular analysis of 20 cases.
PG  - 1329-1343
LID - 10.1038/s41379-019-0273-1 [doi]
AB  - Renal medullary carcinoma is a rare but highly aggressive type of renal cancer 
      occurring in patients with sickle cell trait or rarely with other 
      hemoglobinopathies. Loss of SMARCB1 protein expression, a core subunit of the 
      switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, has emerged 
      as a key diagnostic feature of these tumors. However, the molecular mechanism 
      underlying this loss remains unclear. We retrospectively identified 20 patients 
      diagnosed with renal medullary carcinoma at two institutions from 1996 to 2017. 
      All patients were confirmed to have sickle cell trait, and all tumors exhibited a 
      loss of SMARCB1 protein expression by immunohistochemistry. The status of SMARCB1 
      locus was examined by fluorescence in situ hybridization (FISH) using 3-color 
      probes, and somatic alterations were detected by targeted next-generation 
      sequencing platforms. FISH analysis of all 20 cases revealed 11 (55%) with 
      concurrent hemizygous loss and translocation of SMARCB1, 6 (30%) with homozygous 
      loss of SMARCB1, and 3 (15%) without structural or copy number alterations of 
      SMARCB1 despite protein loss. Targeted sequencing revealed a pathogenic somatic 
      mutation of SMARCB1 in one of these 3 cases that were negative by FISH. Tumors in 
      the 3 subsets with different FISH findings largely exhibited similar 
      clinicopathologic features, however, homozygous SMARCB1 deletion was found to 
      show a significant association with the solid growth pattern, whereas tumors 
      dominated by reticular/cribriform growth were enriched for SMARCB1 translocation. 
      Taken together, we demonstrate that different molecular mechanisms underlie the 
      loss of SMARCB1 expression in renal medullary carcinoma. Biallelic inactivation 
      of SMARCB1 occurs in a large majority of cases either via concurrent hemizygous 
      loss and translocation disrupting SMARCB1 or by homozygous loss.
FAU - Jia, Liwei
AU  - Jia L
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Carlo, Maria I
AU  - Carlo MI
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Khan, Hina
AU  - Khan H
AD  - Department of Hematology and Oncology, Lifespan Cancer Institute at the Rhode 
      Island Hospital, Providence, RI, USA.
FAU - Nanjangud, Gouri J
AU  - Nanjangud GJ
AUID- ORCID: 0000-0002-8547-1957
AD  - Molecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center, New 
      York, NY, USA.
FAU - Rana, Satshil
AU  - Rana S
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Cimera, Robert
AU  - Cimera R
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Zhang, Yanming
AU  - Zhang Y
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Hakimi, A Ari
AU  - Hakimi AA
AD  - Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
FAU - Verma, Amit K
AU  - Verma AK
AD  - Albert Einstein College of Medicine, New York, NY, USA.
FAU - Al-Ahmadie, Hikmat A
AU  - Al-Ahmadie HA
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Fine, Samson W
AU  - Fine SW
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Gopalan, Anuradha
AU  - Gopalan A
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Sirintrapun, S Joseph
AU  - Sirintrapun SJ
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Tickoo, Satish K
AU  - Tickoo SK
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Reuter, Victor E
AU  - Reuter VE
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Gartrell, Benjamin A
AU  - Gartrell BA
AD  - Departments of Medical Oncology and Urology, Montefiore Medical Center, Bronx, 
      NY, USA.
FAU - Chen, Ying-Bei
AU  - Chen YB
AUID- ORCID: 0000-0001-5207-3648
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA. cheny@mskcc.org.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190412
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (SMARCB1 Protein)
RN  - 0 (SMARCB1 protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Carcinoma, Medullary/*genetics/metabolism
MH  - Child
MH  - Female
MH  - Genetic Variation
MH  - Humans
MH  - Kidney Neoplasms/*genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - SMARCB1 Protein/*genetics/*metabolism
MH  - Young Adult
PMC - PMC6731129
MID - NIHMS1523944
COIS- Disclosure/Conflict of Interest The authors declare no conflict of interest.
EDAT- 2019/04/14 06:00
MHDA- 2020/07/07 06:00
PMCR- 2019/10/12
CRDT- 2019/04/14 06:00
PHST- 2019/02/12 00:00 [received]
PHST- 2019/03/13 00:00 [accepted]
PHST- 2019/03/12 00:00 [revised]
PHST- 2019/04/14 06:00 [pubmed]
PHST- 2020/07/07 06:00 [medline]
PHST- 2019/04/14 06:00 [entrez]
PHST- 2019/10/12 00:00 [pmc-release]
AID - S0893-3952(22)01020-1 [pii]
AID - 10.1038/s41379-019-0273-1 [doi]
PST - ppublish
SO  - Mod Pathol. 2019 Sep;32(9):1329-1343. doi: 10.1038/s41379-019-0273-1. Epub 2019 
      Apr 12.