Interestingly, in view of the molecular similarities between blue nevi and uveal melanoma, loss of BAP1
staining in this context appears to be a strong marker of malignancy.
For instance, monosomy of chromosome 3 and gain of 8q are often found in UMs., Multiple common driver mutations have also been identified in UM including BAP1
, EIF1AX , GNA11 , GNAQ , and SF3B1 .,, Specifically, BAP1
, EIF1AX , and SF3B1 mutations are mutually exclusive during UM progression, and BAP1
mutations showed the most significant association with UM metastasis. Meanwhile, epigenetic alteration such as changes in microRNAs and long ncRNAs also plays a role in the development and metastasis of UMs.,
These initial observations have been later completed by the identification of other genetic alterations, such as DAL-1, TRAF7, AKT1, KLF4, PTCH1, SMARCE1, BAP1
, SMO, and PIK3CA mutations [4, 5].
MIAMI -- Although rare, patients who present with one or more skin cancers characteristic of those associated with loss of the BAP1
tumor suppressor protein may be at elevated risk for more aggressive uveal melanomas and other cancers such as kidney cancer and mesothelioma.
Gutierrez, "Effectiveness of batimastat, a synthetic inhibitor of matrix metalloproteinases, in neutralizing local tissue damage induced by BaP1
, a hemorrhagic metalloproteinase from the venom of the snake Bothrops asper," Biochemical Pharmacology, vol.
In human, four UCHs are grouped into smaller UCHs (UCH-L1 and UCH-L3) that prefer to cleave small leaving groups from the C-terminal of Ub and larger UCHs (UCH37 and BAP1
) that hydrolyze polyubiquitin chains .
In humans, four ubiquitin carboxy-terminal hydrolase (UCH) proteins (UCH-L1, UCH-L3, UCH37/uCh-L5, and BAP1
) have been identified, but only UCH-L1 and L3 have been studied in detail .
It also has been reported that several tumor suppressor genes, including BRD7, BAP1
, GATA, CLOCK, and PTPN12, might be potential targets of the miR-200 family [51, 52].
These include highly penetrant genes such as VHL, MET, BAP1
, and FLCN where individuals develop RCC at young ages, and have a family history suggestive of an inherited etiology.
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.
Other characteristics, including genomic factors such as BAP1
mutations , have been suggested as related to survival but are beyond the scope of the SEER national database used here.