High prevalence of p53 exon 4 mutations in soft tissue sarcoma

Abstract

Objective The contribution of genetics to osteoarthritis (OA) progression is not known. To gain more insight into whether familial factors play a role in disease progression of OA, we analyzed familial aggregation of radiologic OA progression in a study of sibling pairs (the Genetics, Arthrosis, and Progression [GARP] study). Methods A total of 105 white probands and their 105 siblings with OA at multiple joint sites were included in a prospective cohort study. Radiologic progression of OA was defined as a 1‐point score increase in total scores for severity of joint space narrowing (JSN) or osteophytes on standardized radiographs of the hands, knees, and hips obtained at baseline and after 2 years. Odds ratios were calculated for siblings and probands sharing radiologic disease progression. Results A total of 100 probands and 93 siblings were followed for 2 years (median age 60 years, 80% women). In 92 sibling pairs both the proband and sibling had complete radiographic followup. Radiologic progression of JSN and osteophytes was present in 47% and 42% of the probands and 34% and 37% of the siblings, respectively. The odds ratios (95% confidence intervals), adjusted for age, sex, and body mass index, of a sibling having radiologic progression if the proband had progression were 3.0 (1.2–7.8) for JSN progression and 1.5 (0.6–3.6) for osteophyte progression. A dose‐response relationship was found between the amount of increase in JSN total scores among probands and the progression of JSN in siblings. Conclusion Familial factors played a role in the radiologic progression of JSN over 2 years in patients with OA at multiple sites.

Tumor suppressor gene alterations of spontaneously malignant transformed cells from human embryonic muscle in vitro

“…Our results were totally different from the p53 mutation database published (30)(31)(32)(33). In particular, the sequence of intron 7 of p53 in our hEMTCs is completely altered, this is different from the mutation type of p53 which is mainly point mutation in malignant cells (37)(38)(39)(40)(41)(42). The alterations of p53 codon region will definitely change the transcription and expression of p53 protein in hEMTCs.…”

Immunohistochemical and Biogenetic Features of Diffuse-Type Tenosynovial Giant Cell Tumors: The Potential Roles of Cyclin A, P53, and Deletion of 15q in Sarcomatous Transformation

“…Nevertheless, we could not detect intragenic mutations in hotspot exons 5 to 9 of the TP53 gene in pure sarcoma cells of any malignant D-TSGCT. Recently, Das et al showed that soft tissue sarcomas might have a higher prevalence of TP53 exon 4 mutations than previously thought (29). Accordingly, the possibility of mutations outside the classical core-binding domain of TP53 could not be completely excluded in malignant D-TSGCTs (27,28,30).…”

Immunoglobulin G is present in a wide variety of soft tissue tumors and correlates well with proliferation markers and tumor grades

“…[23][24][25][26][27][28][29][30] Musella et al demonstrated that cyclin D1 overexpression was an independent factor for survival in patients with sarcoma, 11 and their results were confirmed in other reports. 13,31,32 Although some investigators have demonstrated an inverse correlation between p53 immunopositivity and survival in patients with sarcoma, 9,[33][34][35] more have demonstrated that p53 has no association with patient prognosis. 13,23,26,[36][37][38][39] In the current study, clinical follow-up data on the patients with sarcoma was insufficient to establish a meaningful correlation between clinical outcome and Ig expression.…”

“…Among these, p53 and proliferation markers, including PCNA, Ki-67 (MIB-1), and cyclin D1, have been investigated. [8][9][10][11] These 3 proliferation markers and p53 were chosen for use in the current study on the basis of their previous application in sarcomas and the underlying cell biology of these markers.…”