Aneuploidy is associated with TP53 expression but not with BRCA1 or TERT expression in sporadic colorectal cancer.
BACKGROUND
Defective expression of genes involved in mitotic chromosome segregation (e.g. AURKA, BUB1B), DNA damage response (e.g. TP53, BRCA1), and telomere function (e.g. TERT) may play a role in the development of tumor aneuploidy.


METHODS
The levels of TP53, BRCA1 and TERT were assessed in 55 sporadic colorectal tumors and 37 normal mucosas using tissue microarrays and immunohistochemical detection, and their associations with DNA aneuploidy, levels of mitotic spindle proteins AURKA, AURKB, MAD2L1 and BUB1B and clinicopathological parameters were investigated.


RESULTS
DNA aneuploidy was associated only with TP53 alterations. BRCA1 expression in tumors was significantly correlated with individual mitotic spindle protein expressions, and TERT and MAD2L1 expressions were moderately correlated in the tumor group, suggesting a putative role for TERT in MAD2L1 regulation.


CONCLUSIONS
Loss of TP53 function appears to be involved in the development of aneuploidy, but not in the deregulation of mitotic spindle protein function.
Schjølberg
Aasa R
AR
The Pathology Clinic, Oslo University Hospital - Rikshospitalet, 0027 Oslo, Norway.
Clausen
Ole Petter F
OP
Burum-Auensen
Espen
E
De Angelis
Paula M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics; D001706:Biopsy; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D064246:Mad2 Proteins; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; C509186:TERT protein, human; D019098:Telomerase