Sarcoma is a rare and heterogeneous type of
cancer with an early mean onset age and a poor prognosis. However, its genetic basis remains unclear. A series of recent genomic studies in
sarcomas have identified the occurrence of mutations in the α-
thalassemia/
mental retardation syndrome X-linked (ATRX) gene. The
ATRX protein belongs to the SWI/SNF family of chromatin remodeling
proteins, which are frequently associated with α-
thalassemia syndrome.
Cancer cells depend on
telomerase or the alternative lengthening of telomeres (ALT) pathway to overcome replicative programmed mortality. Loss of ATRX is associated with ALT in
sarcoma. In the present review, recent whole genome and/or whole exome genomic studies are summarized. In addition ATRX immunohistochemistry and ALT fluorescence in situ hybridization in
sarcomas of various subtypes and at diverse sites, including
osteosarcoma,
leiomyosarcoma,
liposarcoma,
angiosarcoma and
chondrosarcoma are evaluated. The present review involves certain studies associated with the molecular mechanisms underlying the loss of ATRX controlling the activation of ALT in
sarcomas. Identification of the loss of ATRX and ALT in
sarcomas may provide novel methods for the treatment of aggressive
sarcomas.