ABSTRACT
INCIDENCE: Soft tissue sarcoma accounts for a approximately 1% of all cancers. Excluding Kaposi sarcoma, the incidence of soft tissue sarcoma has remained stable in Europe (3-4/100,000). ENDOGENOUS FACTORS: Endogenous factors are related to rare genetic syndromes (Li-Fraumeni syndrome, neurofibromatosis, Werner syndrome, bilateral retinoblastom). EXOGENOUS FACTORS: Exogenous factors associated with soft tissue sarcoma are essentially iatrogenic: radiation therapy (prevalence of radiation-induced sarcoma: 0.17-0.21%) and chronically edematous arms after radical mastectomy for breast cancer (Stewart-Treves syndrome). Many studies suggest that environmental or occupational exposure to chlorophenol, phenoxy-herbicides or dioxin increase the risk of soft tissue sarcoma. FURTHER RESEARCH: Little is known about the epidemiology of soft tissue sarcoma. Case-control studies are needed.
Subject(s)
Sarcoma/epidemiology , Sarcoma/etiology , Soft Tissue Neoplasms/epidemiology , Soft Tissue Neoplasms/etiology , Adult , Aged , Arm/pathology , Breast Neoplasms/surgery , Edema/complications , Edema/etiology , Environmental Exposure , Female , Genetic Predisposition to Disease , Humans , Incidence , Male , Mastectomy/adverse effects , Middle Aged , Occupational Exposure , Risk Factors , Xenobiotics/adverse effectsABSTRACT
An asymptomatic shortened variant of protein 4.1 (-8.5 Kd) was first recognized in the red blood cells and designated protein 4.1 Presles. We show here that the missing segment belongs to the 22/24 Kd domain. Protein 4.1 cDNA from reticulocytes was amplified, mapped, and sequenced. The truncation appeared to result from the prevalent skipping of an individual and alternatively spliced exon, also called motif II, whereas this motif is preferentially retained under normal conditions. The same phenomenon was observed in lympho-blastoid cells. Sequencing over 80 bp of intronic sequences 5' and 3' of motif II failed to reveal any change. A new alternative splice site was incidently found 81 nucleotide downstream of motif II in both normal and truncated 4.1 mRNA.
Subject(s)
Exons , Membrane Proteins/genetics , Mutation , Amino Acid Sequence , Base Sequence , Codon/genetics , DNA/genetics , Female , Humans , Male , Molecular Sequence Data , Oligodeoxyribonucleotides , Pedigree , Peptide Mapping , Polymerase Chain Reaction , RNA, Messenger/blood , RNA, Messenger/genetics , RNA, Messenger/isolation & purification , Restriction Mapping , Reticulocytes/metabolismABSTRACT
4.1(-) hereditary elliptocytosis (HE) is a variety of elliptocytosis resulting from the reduction (heterozygosity) or the absence (homozygosity) of protein 4.1. It is nearly always encountered in its heterozygous form. It has been found among Caucasians and North Africans in a sporadic fashion. We report the study on nine family cases of 4.1(-) HE. They were recruited independently (to the exclusion of any other variety of HE) in a limited area around the city of Annecy (French Northern Alps). The mode of genetic transmission, as well as the clinical, morphologic, and protein phenotypes fully conformed to the classical description. Western blots ruled out the existence of any protein 4.1 species of abnormal size. No obvious DNA rearrangement was detectable in any of the nine families with three 4.1 cDNA probes covering the entire coding sequence and part of the flanking 5' and 3' untranslated sequences. On the basis of five polymorphic sites (Bgl II, 2; Pvu II, 3), we found five different haplotypes in normal members of the 4.1(-) families. 4.1(-) HE was associated with the most common haplotype in all the propositi. 4.1 mRNA was studied in four families. Dot-blot hybridization experiments and Northern blots failed to show any detectable change in three families. On the other hand, they showed a 2-kb deletion in the 4.1(-) messenger RNA 5'-moiety in one family. These findings emphasize the heterogeneity of 4.1(-) HE at the molecular level.