This document discusses detecting p53 germline mutations in families with Li-Fraumeni syndrome (LFS). LFS is an autosomal dominant familial cancer syndrome where affected individuals often develop sarcomas before age 45 and have relatives with other cancers. Around 70% of LFS cases are caused by mutations in the p53 gene. Sequencing and single strand conformation polymorphism analysis can be used to detect p53 germline mutations in LFS families. These techniques may help understand the increased cancer risk in families caused by inherited defects in tumor suppressor genes like p53.

1. JURNAL KEDOKTERAN YARSl10 ( 1 ) :39-44 (2002)
Deteksi mutasi Gen p53 germline pada keluarga sindrom
Li-Fraumeni
Detection of p5.3 germline mutation in Li-Fraumeni syndrome
families
Yuni Ahda' dan N. Suhanaa
'Biomedical Postgraduate Programme, Universiry of Indonesia, Jakarta
'Department of Biology, University of Indonesia School of Medicine, Jakarta
KEYWORDS Li-Fraumenisyndrome,p53 germline, SSCP
ABSTRACT Li-Fraumeni syndrome is an autosomal dominantfamilial cancer syndrome that
in its classicform is defined by the existence of both a proband with a sarcoma
and two other first-degree relatives with a cancer by age 45 years. Approximately
70% offamilies with LFS is caused by p53 gene mutation. P53 mutant could not
do its normal function to arrest at GI phase of cell cycles or to induce the cell
death program via apoptosis after DNA damage and thereby may attempt
replication of damaged genome. Thisactivity suggests that cells with mutant p53
will accumulate further mutations more rapidly and display increases genomic
instability. This condition is consistent with the increased neoplastic potential of
patients with Li-Fraumeni syndrome who inherit a germ line defect in one p53
allele.
Sequencing technique is a rapid detection procedure has been developed to detect
the p53 germ line mutation in Li-Fraumenisyndromefamily, but because it is so
labor intensive, large-scale screening tests are impractical. Some alternative
techniques have been developed like functional screening test of p53 mutation
based on the loss of wild type transcription activation and single strand
conformation polymorphism mutation analysis based on the diferences of single
strand DNA migrationpattern on polyac ylamide gel.
Biologi molekuler sebagai salah satu seseorangatau suatu keluarga terkena kanker.
cabangilmu yang relatif baru telah diterapkan Ada banyak gen supresor tumor yang
secara luas dalam berbagai bidang penelitian terdeteksi terlibat dalam perkembangan
termasuk penelitian di bidang kesehatan kanker dan salah satunya adalah gen supresor
klinis. Salah satu penelitian klinis yang tumor p53. Mutasi gen p53 g-epertama
melibatkan aspek molekuler adalah penelitian kali terdeteksi pada sindrom Li-Fraurneni
dalam bidang kanker. Biologi molekuler (LFS), yaitu suatu sindrom kanker keluarga
dewasa ini dapat digunakan untuk menelu- yang bersifat dominan autosom yang secara
suri kecenderungan penurunan kanker dalam sederhana ditandai dengan terdapatnya lebih
satu keluarga. Hal ini dimungkinkan dengan - -
pendeteksianmutasi-mutasieermline.
Salah satu mutasi germline yang banyak
dibicarakan adalah mutasi pada gen supresor
tumor yang meningkatkan kecenderungan
Yuni Ahda, S.Si, M.Kes. Biomedical Postgraduate Programme,
Universityof Indonesia,School of Medicine,JaIan Salemba Raya 6,
Jakarta 10430, Telephone: (021) 330379, email: