1) Definizione del paziente e della storia
Anno di nascita : 1941
Peso: 78 Statura: 1,78 BMI: 27,3
Anamnesi patologica prossima
2001 carcinoma spinocellulare della tonsilla; irradiato
Anamnesi patologica remota
14 anni: trauma da sci
26 anni: aborto al 6 mese
28 anni: inizio cefalea
42 anni: menopausa
in tal modo la sequenza temporale degli eventi è chiara e il legame con l'età è istintivo.
2) Le basi molecolari degli eventi descritti, tenendo conto di tutti i sintomi ed utilizzando i link alle informazioni pertinenti
HPV associato certamente a carcinomi spinocellulari, possibilmente anche a BCLL (un mio caso personale)
Methylenetetrahydrofolate reductase (MTHFR) gene 677C>T and 1298A>C polymorphisms are associated with differential apoptosis of leukemic B cells in vitro and disease progression in chronic lymphocytic leukemia.2004
Delezione 13q14.3 72% marzo 2006, 16% maggio 2007
Trisomia 12p11.1-q11.1 da marzo 2005 (16%) a<1% aprile 2006
Subclinical chronic lymphocytic leukaemia associated with a 13q deletion presenting initially in the skin: apropos of a case. 2006
Human RFP2 gene promoter: unique structure and unusual strength.
Human gene RFP2 is a candidate tumor suppressor located at 13q14.3 and deleted in multiple tumor types. To explore regulation of RFP2, we determined structure of the 5'-untranslated region of RFP2 gene and its promoter. RFP2 promoter area is TATA-less, highly enriched in G and C nucleotides, and contains multiple quadruplex forming GGGGA-repeats. Deletion analysis of 5'-flanking sequences demonstrated that repeat containing fragment possesses activity seven times exceeding that of the combined SV40 promoter/enhancer. Other unusual features of the RFP2 promoter include anomalously high electrostatic fields induced by sequence-dependent dipoles and very low nucleosome forming potential. A "minimized" version of the RFP2 promoter could be used for overexpression of the various transgenes in the mammalian cells.
13q deletion in chronic lymphocytic leukemia: characterization of E4.5, a novel chromosome condensation regulator-like guanine nucleotide exchange factor.
We report the characterization of a new gene (E4.5) that maps at chromosome band 13q14.3, a chromosomal area frequently deleted in chronic lymphocytic leukemia (CLL) and in other lymphoid malignancies. E4.5 gene encodes for a 4 kb mRNA expressed in various tissues and has an open reading frame of 531 amino acids. The predicted E4.5 protein shows strong homology with the human regulator of chromosome condensation (RCC1) protein, the principal GTP exchange factor for Ran protein. The E4.5 protein contains a BTB domain in its N-terminus, a protein-protein interaction motif. Therefore, we propose that E4.5 is a new member of the RCC1-related guanine nucleotide exchange factor (GEF) family with potent interaction with other proteins and unknown function. Until now, no tumor suppressor genes have been mapped in the 13q14.3 minimal deleted region (MDR) in patients with CLL. It has been proposed that loss of the 13q14.3 MDR may contribute to lymphoid neoplasia by altering the expression/function of genes located on 13q14.3 outside the MDR. The E4.5 is one of these genes with a potential role in the pathogenesis of CLL.
Genes at 13q14
3) Eventuali proposte di terapia, volta al ripristino delle condizioni ottimali