CDK4 is co-amplified with either TP53 promoter gene fusions or MDM2 through distinct mechanisms in osteosarcoma.

Amplification of the MDM2 and CDK4 genes on chromosome 12 is commonly associated with low-grade osteosarcomas. In this study, we conducted high-resolution genomic and transcriptomic analyses on 33 samples from 25 osteosarcomas, encompassing both high- and low-grade cases with MDM2 and/or CDK4 amplification. We discerned four major subgroups, ranging from nearly intact genomes to heavily rearranged ones, each harbouring CDK4 and MDM2 amplification or CDK4 amplification with TP53 structural alterations.

Disruption of the TP53 locus in osteosarcoma leads to TP53 promoter gene fusions and restoration of parts of the TP53 signalling pathway.

TP53 is the most frequently mutated gene in human cancer. This gene shows not only loss-of-function mutations but also recurrent missense mutations with gain-of-function activity. We have studied the primary bone malignancy osteosarcoma, which harbours one of the most rearranged genomes of all cancers.

Osteosarcomas With Few Chromosomal Alterations or Adult Onset Are Genetically Heterogeneous.

Osteosarcoma is the most common primary bone malignancy, often detected in children and adolescents and commonly associated with TP53 alterations along with a high number of chromosomal rearrangements. However, osteosarcoma can affect patients of any age, and some tumors display less genetic complexity. Besides TP53 variants, data on key driving mutations are lacking for many osteosarcomas, particularly those affecting adults.

Intralesional margin after excision of a high-grade osteosarcoma: Is it a catastrophe?

Background And Objectives: Treatment of high-grade osteosarcoma (OS) relies on a combination of systemic chemotherapy and radical surgical excision of the tumor. Little is known on what happens in case of an irrefutably inadequate (intralesional) margin. We aimed to describe the outcome of patients with high-grade OSs of the trunk and the extremities where planned wide resection resulted in an intralesional margin.

Bone mineral: A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumor eradication with nano hydroxyapatite containing doxorubicin.

Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a cornerstone drug used for osteosarcoma treatment, shows reversible accretion to hydroxyapatite (HA) of both nano (nHA) and micro (mHA) size. nHA particles functionalized with DOX get engulfed in the lysosome of osteosarcoma cells where the acidic microenvironment causes a disruption of the binding between DOX and HA.

Late Local Recurrence and Metastasis in Soft Tissue Sarcoma of the Extremities and Trunk Wall: Better Outcome After Treatment of Late Events Compared with Early.

Background: Approximately 80% of soft tissue sarcoma (STS) recurrences, local and metastatic disease, are diagnosed within the first 3 years after primary diagnosis and treatment. Recurrences, however, can present after a longer period of remission. Our goal was to identify factors that may predict the risk of late recurrence.

Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma.

Osteoblastoma is a locally aggressive tumour of bone. Until recently, its underlying genetic features were largely unknown. During the past two years, reports have demonstrated that acquired structural variations affect the transcription factor FOS in a high proportion of cases.

High Recurrence Rate of Myxofibrosarcoma: The Effect of Radiotherapy Is Not Clear.

Background: Myxofibrosarcoma (MFS) is one of the more common types of soft-tissue sarcoma (STS) in patients over 60 years of age. Local recurrence (LR) rates have been reported to be higher compared to other STS types.

Patients And Methods: Using a population-based series from the southern Sweden health care region, 56 consecutive patients with MFS and localized disease at diagnosis were analyzed with respect to LR and distant metastases after surgery ± adjuvant treatment.

Soft-tissue sarcoma in adolescents and young adults compared with older adults: A report among 5000 patients from the Scandinavian Sarcoma Group Central Register.

Background: In recent years, there has been growing awareness of the distinct characteristics of adolescents and young adults (AYA) diagnosed with cancer. Soft-tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed in adults and 8% of cancers diagnosed in AYA. To the best of our knowledge, only a few sarcoma registers include data regarding histological subtype, age at diagnosis, and detailed clinical information.

[Respiratory failure and neurological impairment in a child with Duchenne muscular dystrophy following minor trauma].

Fat Embolism Syndrome (FES) is a rare and often lethal condition, associated with trauma or surgery. It is more serious than a typical fat embolism seen after a fracture in a long bone. FES is a triad of symtoms, including respiratory failure, abnormal neurology and petechial bleeding.

Ewing sarcoma of the mobile spine; predictive factors for survival, neurological function and local control. A Scandinavian sarcoma group study with a mean follow-up of 12 years.

Many patients with Ewing sarcoma (ES) of the mobile spine present with neurologic symptoms leading to emergency decompressive surgery. Only rarely is optimal treatment involving neo-adjuvant chemotherapy followed by en bloc excision possible. The purpose of this study was to study treatment, neurologic and oncologic outcome in patients with ES of the mobile spine.

The Scandinavian Sarcoma Group Central Register: 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma.

Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables.

Referral patterns, treatment and outcome of high-grade malignant bone sarcoma in Scandinavia--SSG Central Register 25 years' experience.

Aims: The objectives of this study were to present changes in referral patterns, treatment and survival in patients with high-grade malignant bone sarcoma in Sweden and Norway based on data in the Scandinavian Sarcoma Group (SSG) Central Register.

Method: Data on 1,437 patients with diagnosis 1986-2010 was analyzed.

Results: Osteosarcoma was the most frequentl diagnosis (45%), followed by Ewing sarcoma (21%) and chondrosarcoma (17%).

Prognostic factors and follow-up strategy for superficial soft-tissue sarcomas: Analysis of 622 surgically treated patients from the scandinavian sarcoma group register.

Background And Objectives: Our study aimed to describe the clinical outcome of patients with superficial soft-tissue sarcomas (SSTS), define prognostic factors and provide evidence for a rational surveillance scheme.

Methods: Data for 622 consecutive, surgically treated SSTS patients were retrieved from the Scandinavian Sarcoma Group Register. We assessed the rates of local recurrence (LR) and metastasis (M), as well as overall survival (OS), local recurrence free-survival (LRFS) and metastasis-free survival (MFS) of the cohort.

[Most musculoskeletal soft tissue tumors are benign].

Most musculoskeletal soft tissue tumors are benign, lipoma being the most common. Malignant soft tissue tumors may be difficult to clinically distinguish from benign. Scandinavian recommendations are that all lesions suspicious for sarcoma be referred to a sarcoma center.

Key roles for MYC, KIT and RET signaling in secondary angiosarcomas.

Background: Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.

Methods: Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas.

Small soft tissue sarcomas do metastasize: identification of high-risk tumors.

Background: Small (≤ 5 cm) soft tissue sarcomas (STS) of the extremities and the trunk wall generally have a favorable prognosis. However, 1 of 10 patients do develop metastases, and we therefore aimed to determine predictors of metastasis in a population-based cohort of patients with small STSs.

Patients And Methods: In the southern Sweden health care region, 848 adult patients with STS of the extremities or the trunk wall were diagnosed between 1986 and 2010.

Simple guidelines for efficient referral of soft-tissue sarcomas: a population-based evaluation of adherence to guidelines and referral patterns.

Background: Optimal treatment of soft-tissue sarcoma requires multidisciplinary management at a sarcoma center. However, these rare tumors are often misinterpreted as benign and many are inadequately treated outside a sarcoma center, with an increased risk of local recurrence that often requires further extensive surgical treatment. To improve referral and centralization of soft-tissue sarcoma management in the southern Sweden health care region, an open-access outpatient clinic at our sarcoma center and simple referral guidelines have been established for the past thirty years.

Radiation-associated angiosarcoma after breast cancer: high recurrence rate and poor survival despite surgical treatment with R0 resection.

Background: Secondary angiosarcoma of the breast is a rare but severe long-term complication of breast cancer treated with breast-conserving surgery and radiotherapy. We characterized a population-based cohort of patients with secondary angiosarcomas from two tertiary hospitals to investigate this complication with respect to surgical treatment and outcome.

Methods: We identified 35 patients with a history of radiation for breast cancer that developed angiosarcoma in the irradiated field from 1990 to 2009.

Delays in the management of retroperitoneal sarcomas.

Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method.

Changing clinical presentation of angiosarcomas after breast cancer: from late tumors in edematous arms to earlier tumors on the thoracic wall.

Angiosarcoma is a rare complication of breast cancer treatment. In order to define predictors, clinical presentation, and outcome, we characterized a population-based 50-year cohort of angiosarcomas after breast cancer. Clinical data were collected from all females with previous breast cancer who developed angiosarcomas/lymphangiosarcomas on the thoracic wall/upper extremity between 1958 and 2008 in the Southern Swedish health care region.