CPL - Chalmers Publication Library
| Utbildning | Forskning | Styrkeområden | Om Chalmers | In English In English Ej inloggad.

Mutations in the N-terminal domain of DFF45 in a primary germ cell tumor and in neuroblastoma tumors.

Frida Abel ; Rose-Marie Sjöberg ; Cecilia Krona ; Staffan Nilsson (Institutionen för matematisk statistik) ; Tommy Martinsson
International journal of oncology (1019-6439). Vol. 25 (2004), 5, p. 1297-302.
[Artikel, refereegranskad vetenskaplig]

DFF45 has essential functions in the final stage of apoptosis by acting both as a folding chaperone and a DNase inhibitor of DFF40. The gene encoding DFF45 (DFFA) maps to the consensus deleted region in primary neuroblastoma (NB; 1p36.2-3) and within the homozygously deleted region in an NB cell line (1p36.2). DFF45 is therefore an attractive candidate NB tumor suppressor. In a previous study we found a rare allele variant, causing a non-polar to a polar amino acid exchange (Ile69Thr) in a preserved hydrophobic patch of DFF45, and we also found DFFA to be preferentially expressed in favorable NB tumors. We have extended the previous study and performed mutation analyses in another 56 NB tumors (100 in total) as well as a set of other tumors for coding mutations in DFFA. We have also performed studies of the DFFA expression in tumors using real-time PCR. We found a missense mutation (Ile15Met) in the remaining allele of a teratoma with heterozygous deletion of 1p, and a three base-pair deletion in an NB of unknown stage causing a deletion of amino acid 37 in DFF45. The one-base substitution detected in the teratoma was not present in the patients constitutional DNA, i.e. it is a true mutation present in the tumor DNA only. In conclusion, three different coding alterations have been found in the region encoding the N-terminal regulatory domain of DFF45, responsible for binding and achieving its chaperone and inhibitor functions on other proteins. Moreover, by real-time RT-PCR expression study, we found the mRNA level of DFFA to be significantly (p=0.038) reduced by a factor of 1.7 times in NB tumors of unfavorable outcome.

Nyckelord: Apoptosis, Apoptosis Regulatory Proteins, DNA Mutational Analysis, Deoxyribonucleases, genetics, Humans, Intracellular Signaling Peptides and Proteins, Mutation, Missense, Neoplasm Staging, Neoplasms, Germ Cell and Embryonal, genetics, Neuroblastoma, genetics, Prognosis, RNA, Messenger, analysis, Reverse Transcriptase Polymerase Chain Reaction

Denna post skapades 2007-10-08. Senast ändrad 2015-01-16.
CPL Pubid: 52079


Läs direkt!

Länk till annan sajt (kan kräva inloggning)

Institutioner (Chalmers)

Institutionen för kvinnors och barns hälsa, Avdelningen för pediatrik (1991-2005)
Institutionen för matematisk statistik (2002-2004)



Chalmers infrastruktur