Abstract
BACKGROUND
Partially due to the rare occurrence of soft tissue and osteogenic sarcomas in the general population, scant attention has been given to their hereditary etiology. Their overall poor prognosis might be ameliorated through an understanding of their environmental and hereditary causal factors, and/or their interactions, thereby contributing to earlier diagnosis and even the development of molecularly based targeted therapy.
METHODS
The authors selected 10 sarcomaโprone families from their extensive hereditary cancerโprone family resource and focused on their challenging diagnostic, surveillance, and management features. The family study protocol included the compilation of a detailed family history of malignant disease of all anatomic sites and the collection of all available primary medical and pathology documents for verification. Genetic counseling was provided before DNA collection and at disclosure of results.
RESULTS
These families displayed marked phenotypic and genotypic heterogeneity. In one of these families, 16 relatives had sarcomas, with 2 of the 16 each having 2 metachronous sarcomas; to our knowledge, this represents the greatest number of sarcomas reported in any family described to date. Two familial atypical multipleโmole melanoma syndrome kindreds with the CDKN2A mutation showed the association of sarcoma with malignant melanoma, whereas one family had several pancreatic carcinomas. Other families with sarcoma had hereditary nonpolyposis colorectal carcinoma with MSH2 mutation, hereditary breast carcinoma with BRCA1 mutation, and p53 mutation in a LiโFraumeni syndrome.
CONCLUSIONS
Sarcomaโprone families reported in the current study were selected carefully to depict clinicopathology and compliance features, the understanding of which could elucidate the etiologic role of genetic factors in concert with the phenotypic and genotypic heterogeneity encountered in such families. The lack of a populationโbased data set for these families posed a limitation. Cancer 2003. ยฉ 2003 American Cancer Society.