Loss of p16INK4A expression is associated with allelic imbalance/loss of heterozygosity of chromosome 9p21 in microdissected synovial sarcomas.
Deletions of the short arm of chromosome 9 have been observed in many tumours and cell lines. This chromosomal region is frequently targeted during malignant transformation because it contains at least two known tumour suppressor genes: p16(INK4) and p15(INK4B). p16(INK4A) acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein and therefore block the progression of the cell cycle from G1 to S phase. The role of p16(INK4A) in the development of synovial sarcoma has not been comprehensively investigated. Ten samples of synovial sarcomas were examined for allelic imbalance/loss of heterozygosity (AI/LOH) of the 9p region and p16 protein expression. DNA was isolated from microdissected sections of normal and tumour cells, amplified by polymerase chain reaction and analysed for AI/LOH by using six microsatellite markers that map to the 9p region. Immunohistochemistry for p16 expression was done. AI/LOH with at least one microsatellite marker on 9p21 was detected in six of ten samples. The most frequent allelic deletions were observed within the coding sequence of p16(INK4A). Loss of p16 immunoreactivity was detected in eight samples, six of which showed evidence of alterations at 9p21 region. These findings suggest a possible role of loss of p16(INK4A) in the development of synovial sarcoma.
Sabah
Muna
M
Department of Histopathology, Education and Research Centre, The Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. munasabah@eircom.net
Cummins
Robert
R
Leader
Mary
M
Kay
Elaine
E
D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D042282:Microdissection; D016133:Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm