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PubMed2004

The combination of p53 mutation and neu/erbB-2 amplification is associated with poor survival in node-negative breast cancer.

PURPOSE: Increases in neu/erbB-2 have been implicated in breast cancer prognosis, but do not predict all recurrences. On the basis of evidence that p53 mutation is involved in the development of human neoplasia, we examined the prognostic value of p53 alterations in combination with neu/erbB-2 amplification. PATIENTS AND METHODS: A consecutive series of women were observed for recurrence and death (median follow-up of 85 months) and tumors from 543 individuals were analyzed for p53 mutation status and neu/erbB-2 amplification. Exons 4 through 10 of the p53 gene were analyzed by single-stranded conformational polymorphism and mutations were confirmed by DNA sequencing. The association of p53 mutation status and neu/erbB-2 amplification with risk of recurrence and death was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: p53 mutations occurred in 24.5% of the axillary node-negative breast carcinomas. Mutations were more frequent in carcinomas with neu/erbB-2 amplification: 38.9% compared with only 20.9% in those without neu/erbB-2 amplification. We found elevated risks of disease recurrence and overall mortality in patients with both p53 mutation and neu/erbB-2 amplification in their tumor compared with patients with neither or only one of the alterations. This increase persisted with adjustment for other prognostic factors (relative risk, 2.32; P =.002 for recurrence; relative risk, 2.22; P =.004 for death). CONCLUSION: Evaluation of tumors for p53 mutations may be beneficial to identify women at higher risk of disease recurrence and death when the tumor has neu/erbB-2 amplification, but in the absence of neu/erbB-2 amplification, the presence of p53 mutation may not provide additional independent prognostic information.

Adult↗
PubMed2004

Molecular analysis of the eighteen most frequent mutations in the BRCA1 gene in 63 Chilean breast cancer families.

BRCA1 gene mutations account for nearly all families with multiple cases of both early onset breast and/or ovarian cancer and about 30% of hereditary breast cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and variants have been described, several mutations have been found to be recurrent in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns in which these mutations are located was made using mismatch PCR assay, ASO hybridization assay, restriction fragment analysis, allele specific PCR assay and direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G) and one variant of unknown significance (E1250K) were found in four of these families. Also, a new mutation (4185delCAAG) and one previously described polymorphism (E1038G) were found in two other families. The 185delAG was found in a 3.17% of the families and the others were present only in one of the families of this cohort. Therefore these mutations are not prominent in the Chilean population. The variant of unknown significance and the polymorphism detected could represent a founder effect of Spanish origin.

Breast Neoplasms↗
PubMed1994

[Physiology and pathophysiology of the metabolism of lipoproteins].

UNLABELLED: PHYSIOLOGY: Lipoproteins (LP) are generally classified according to their density. Triglycerides are mainly transported in chylomicrons and very low density LP (VLDL), cholesterol is mainly transported in low density LP (LDL) and high density LP (HDL). The metabolism of LP is controlled by their apolipoproteins, by specific receptors, enzymes, and transfer proteins. Triglycerides and cholesterol from the diet are transported in chylomicrons. The triglycerides are rapidly hydrolyzed by LP-lipase to yield chylomicron remnants. The released free fatty acids are used either for storage in adipose tissue or for oxidation in other tissues. Dietary cholesterol is transported in the chylomicron remnants to the liver. Cholesterol and triglyceride are also synthesized in the liver and then secreted into the blood in the form of VLDL. VLDL triglycerides are metabolized by LP-lipase to intermediate density LP (IDL), which are either taken up by the liver or further catabolized to LDL. LDL are bound and taken up by specific receptors (LDL receptors) in the liver and many other tissues. By this pathway, cholesterol is transported from the liver to peripheral tissues. LDL can be modified by oxidation and then taken up by macrophages in the arterial intima resulting in the formation of foam cells, an important step in atherogenesis. HDL play an important role in reverse cholesterol transport (transport of cholesterol back to the liver, the only site of cholesterol excretion). PATHOPHYSIOLOGY: Various mutations in the LP-lipase gene or in the apo C-II gene result in LP-lipase deficiency. Homozygous carriers of the mutated gene show defective metabolism of chylomicrons and VLDL with extreme hypertriglyceridemia, eruptive xanthomas, hepatosplenomegaly and recurrent bouts of acute pancreatitis. Many mutations in the LDL receptor gene have been described as the primary cause of familial hypercholesterolemia due to LDL receptor deficiency. LDL receptor deficiency results in the accumulation of LDL in the plasma and deposition of LDL cholesterol in tendons and skin (xanthomas) and arteries (atheromas). In homozygotes, coronary heart disease begins in childhood. Familial defective apo B-100 is caused by a mutation in codon 3500 of the apo B gene. LDL with the mutated apo B is not recognized by the LDL receptor and LDL accumulates in the blood. Mutant forms of apo E (apo E-2 and others) are not bound to the LDL(B,E)-receptor resulting in accumulation of chylomicrons and VLDL remnants (beta-VLDL) and IDL. For the manifestation of type III hyperlipemia, additional genetic, hormonal or environmental factors are involved. Cholesterol deposition in macrophages of the arterial intima and skin gives rise to atherosclerosis of coronary and peripheral arteries and xanthomas. The pathogenesis of familial combined hyperlipemia, the most frequent form of primary hyperlipemias, is multifactorial and has not been clarified in detail.

Humans↗
PubMed2004

Effective long-term control of cardiac events with beta-blockers in a family with a common LQT1 mutation.

The congenital long QT syndrome (LQTS) is characterized by a prolonged QT interval on the surface electrocardiogram and an increased risk of recurrent syncope and sudden cardiac death. Mutations in seven genes have been identified as the molecular basis of LQTS. beta-blockers are the treatment of choice to reduce cardiac symptoms. However, long-term follow-up of genotyped families with LQTS has been rarely reported. We have clinically followed a four-generation family with LQTS being treated with beta-blocker therapy over a period of 23 years. Seven family members were carriers of two amino acid alterations in cis (V254M-V417M) in the cardiac potassium channel gene KCNQ1. Voltage-clamp recordings of mutant KCNQ1 protein in Xenopus oocytes showed that only the V254M mutation reduced the IKs current and that the effect of the V417M variant was negligible. The family exhibited the complete clinical spectrum of the disease, from asymptomatic patients to victims of sudden death before beta-blocker therapy. There was no significant reduction in QTc (556 +/- 40 ms(1/2) before therapy, 494 +/- 20 ms(1/2) during 17 years of treatment; n = 5 individuals). Of nine family members, one female died suddenly before treatment, three females of the second generation were asymptomatic, and four individuals of the third and fourth generation were symptomatic. All mutation carriers were treated with beta-blockers and remained asymptomatic for a follow-up up to 23 years. Long-term follow-up of a LQT1 family with a common mutation (V254M) being on beta-blocker therapy was effective and safe. This study underscores the importance of long-term follow-up in families with specific LQT mutations to provide valuable information for clinicians for an appropriate antiarrhythmic treatment.

Adrenergic beta-Antagonists↗
PubMed1991

The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: heterogeneity and founder effects.

Heterozygosity for protein C deficiency is associated with thromboembolic episodes, but clinical symptoms are nonrandomly distributed among protein C deficient families. This finding has led to the provisional definition of clinically dominant and clinically recessive protein C deficiency. We report here the molecular basis of hereditary, clinically dominant protein C deficiency in a panel of 40 Dutch probands from apparently independent families. All but one subject was a heterozygote for a point mutation in the protein C gene. These 39 subjects shared 15 mutations, six of which occurred in more than one proband (between two and nine). The diversity in the 15 mutations, together with the observation that the most frequent Dutch mutation was also found in a Swedish family with clinically recessive protein C deficiency, makes it unlikely that the molecular basis of protein C deficiency will be different between the clinically dominant and recessive forms. The recurrence of one of the mutations is most likely due to a founder effect, which suggests that when an additional hereditary factor is involved in the clinical severity of protein C deficiency this factor may remain linked to the protein C gene over many generations.

Base Sequence↗
PubMed2006

McArdle disease: the mutation spectrum of PYGM in a large Italian cohort.

Deficiency of the muscle isozyme of glycogen phosphorylase is causative of McArdle disease or Glycogen storage disease type V (GSD-V), the most common autosomal recessive disorder of glycogen metabolism. The typical clinical presentation is characterized by exercise intolerance with cramps, and recurrent myoglobinuria. To date, 46 mutations in the PYGM gene have been detected in GSD-V patients. We report the mutational spectrum in 68 Italian patients. We identified 30 different mutations in the PYGM gene, including 19 mutations that have not been reported previously. The novel mutations include: eight missense mutations (c.475G>A, p.G159R; c.689C>G, p.P230R; c.1094C>T, p.A365E; c.1151C>A, p.A384D; c.1182C>T, p.R428C; c.1471C>T, p.R491C; c.2444A>C, p.D815A; c.2477G>C, p.W826S), two nonsense mutations (c.1475G>A, p.W492X; c.1627A>T, p.K543X), five splice site mutations (c.855 +1G>C; c.1092 +1G>A; c. 1093-1G>T; c.1239 +1G>A; c.2380 +1G>A), and four deletions (c.715_717delGTC, p.V239del; c.304delA, p.N102DfsX4; c.1970_2177del, p.V657_G726; c.2113_2114delGG, p.G705RfsX16). Whereas we confirmed lack of direct correlation between the clinical phenotype and the genotype, we also found that the so-called 'common mutation' (p.R50X) accounted for about 43% of alleles in our cohort and that no population-related mutations are clearly identified in Italian patients.

Adolescent↗
PubMed1992

Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen. The mosaic parent exhibits phenotypic features of a mild form of the disease.

We have determined that a man, ascertained because he fathered a child with lethal osteogenesis imperfecta (OI) with each of two partners, is mosaic in both his germline and somatic tissues for a mutation in the COL1A2 gene which encodes the pro alpha 2(I) chain of type I procollagen. His dermal fibroblasts were previously shown to synthesize a population of cysteine-containing alpha 2(I) chains that were posttranslationally overmodified. DNA sequence analysis of COL1A2 cDNAs demonstrated that the cysteine-containing chain resulted from a point mutation (G to T) in the first position of the codon for the glycine at residue 472 of the triple helical domain. Genomic DNA from the one available affected infant contained the mutant and normal COL1A2 alleles in equal proportion. Examination of DNA from several tissues of the father showed that the mutant allele was present in approximately 40% of his sperm, 80% of his lymphocytes, and nearly 100% of his dermal fibroblasts. Despite the high level of mosaicism detected in somatic tissues, the only phenotypic manifestation of OI in the proband was that he was shorter than his unaffected male relatives and had mild dentinogenesis imperfecta. Thermal stability of type I collagen molecules containing the substitution was decreased, but to a lesser extent than for a nonlethal cysteine for glycine substitution at residue 259 of alpha 2(I), indicating that this measure of molecular stability may be of limited use in explaining the pathogenesis of osteogenesis imperfecta.

Adult↗
PubMed2004

Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome.

Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant NS (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes of ESRD in the first two decades of life. Mutations in the NPHS2 gene represent a frequent cause of SRNS, occurring in approximately 20 to 30% of sporadic cases of SRNS. On the basis of a very small number of patients, it was suspected that children with homozygous or compound heterozygous mutations in NPHS2 might exhibit primary steroid resistance and a decreased risk of FSGS recurrence after kidney transplantation. To test this hypothesis, NPHS2 mutational analysis was performed with direct sequencing for 190 patients with SRNS from 165 different families and, as a control sample, 124 patients with steroid-sensitive NS from 120 families. Homozygous or compound heterozygous mutations in NPHS2 were detected for 43 of 165 SRNS families (26%). Conversely, no homozygous or compound heterozygous mutations in NPHS2 were observed for the 120 steroid-sensitive NS families. Recurrence of FSGS in a renal transplant was noted for seven of 20 patients with SRNS (35%) without NPHS2 mutations, whereas it occurred for only two of 24 patients with SRNS (8%) with homozygous or compound heterozygous mutations in NPHS2. None of 29 patients with homozygous or compound heterozygous mutations in NPHS2 who were treated with cyclosporine A or cyclophosphamide demonstrated complete remission of NS. It was concluded that patients with SRNS with homozygous or compound heterozygous mutations in NPHS2 do not respond to standard steroid treatment and have a reduced risk for recurrence of FSGS in a renal transplant. Because these findings might affect the treatment plan for childhood SRNS, it might be advisable to perform mutational analysis of NPHS2, if the patient consents, in parallel with the start of the first course of standard steroid therapy.

Adolescent↗
PubMed1996

Analysis of the cellular origin of hepatocellular carcinoma by p53 genotype.

The polymerase chain reaction and HaeIII enzymatic digestion were used to study the seventh exon of the p53 gene in 29 primary and recurrent hepatomas in paraffin-embedded samples from 11 patients. The mutation rate of the p53 gene and its genotypes in samples of primary and recurrent tumours and multiple nodules were investigated. The cellular origins of hepatocellular carcinoma were analysed by p53 genotype. p53 mutation rates were found to be 69.0% (20/29) in the primary and recurrent tumours, 58.8% (10/17) in tumours with a single nodule and 83.3% (10/12) in tumours with multiple nodules. The p53 genotypes were found to be different in 6 pairs of primary and recurrent tumours, and another 5 pairs had the same p53 genotypes. The samples with multiple nodules in the same patients had the same p53 genotypes. Seven recurrences were of multicentric origin and four were of unicentric origin. It is suggested that the recurrent lesions developed from both unicentric and multicentric origins.

Adult↗
PubMed1999

Isolated sulfite oxidase deficiency: review of two cases in one family.

OBJECTIVE: The authors describe two cases of isolated sulfite oxidase deficiency found in one family. This is a rare autosomal-recessive disorder presenting at birth with seizures, severe neurologic disease, and ectopia lentis. It can be easily missed with metabolic screening; however, the finding of lens subluxation stresses the importance of ophthalmic assessment in making the diagnosis. DESIGN: Two observational case reports. INTERVENTION/METHODS: Ophthalmic assessment, biochemical assay for specific urinary and plasma metabolites, magnetic resonance imaging, and gene sequencing were used to make the diagnosis of the disease in the proband. The diagnosis was subsequently recognized in a previously affected sibling after the postmortem neuropathology was reviewed. Mutation analysis was performed on cultured fibroblasts from the proband to identify and categorize the specific mutation responsible for the disease in the family. From this, future prenatal detection of sulfite oxidase deficiency is possible. MAIN OUTCOME MEASURES: The diagnosis of sulfite oxidase deficiency was established in this family, enabling appropriate genetic counseling and recurrence risk estimation. RESULTS: Point mutations were found in both alleles of the sulfite oxidase gene in the proband. The first is a 623C-->A mutation, which predicts an A208D substitution, and the second is a 1109C-->A, which predicts an S370Y substitution. Both residues A208D and S370Y are critical for sulfite oxidase activity. CONCLUSIONS: Isolated sulfite oxidase deficiency is a rare heritable disease for which mutation analysis can allow accurate prenatal screening. It often is difficult to diagnose by clinical presentation alone, but the critical finding of lens subluxation accompanying seizures and diffuse neurologic disease in an infant should alert the physician to the diagnosis.

Alleles↗
PubMed2004

The role of genomic instability in the pathogenesis of squamous cell carcinoma of the head and neck.

Measurements of genomic instability, or identification of genes responsible for instability, may potentially be used as molecular markers to predict disease course and response to therapy. Other possible applications include use of genomic instability measurements, or genes, as tools to screen for primary or recurrent disease. Methodologies for detection of genetic mutations in saliva, blood, and sputum have already been described[61,62]. Brennan et al [63] have described a molecular technique for analyzing histopathologically negative margins and lymph nodes for the presence of p53 gene mutation. This study showed that a positive molecular margin significantly predicted disease recurrence. The recognition that HNSCC is a genetically heterogeneous disease represents a major step toward developing an understanding of its underlying genetic basis. To develop an insight into this genetically heterogeneous disease, investigators must not only focus their efforts on specific head and neck disease sites. Laser-capture microdissection represents a powerful tool for isolating very specific cell populations from tumors [64]. Leethanakul et al[65] performed laser-capture microdissection on oral cavity SCC to construct stage-specific cDNA libraries. Sequencing of 96 clones from each of the six libraries constructed suggested the existence of 132 novel genes, which may play a role in the pathogenesis of HNSCC. The current literature suggests that many individuals diagnosed withHNSCC are genetically predisposed to developing malignancy because of some inherent deficiency of their capacity to maintain their genome in the presence of environmental stressors. Head and neck cancers are highly heterogeneous tumors and exhibit a wide variety of forms of genomic instability. Thus, genomic instability may be viewed as a fundamental force driving head and neck tumorigenesis and evolution. Future study of the specific genetic mechanisms that underlie genomic instability in the HNSCCpatient population is needed. It is only through study of this fundamental force that drives the development of these tumors that clinicians may gain the insight required to develop new diagnostic and therapeutic modalities to benefit the HNSCC patient population as a whole.

Carcinoma, Squamous Cell↗
PubMed2003

Phototherapeutic keratectomy for BIGH3-linked corneal dystrophy recurring after penetrating keratoplasty.

PURPOSE: To determine visual results and report side effects and complications after phototherapeutic keratectomy (PTK) for BIGH3-linked corneal dystrophy recurring after penetrating keratoplasty. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Forty-two excimer laser PTK procedures were performed in 42 eyes of 29 patients with BIGH3-linked corneal dystrophies. Genetic status of all patients was determined and allowed us to assess an unambiguous diagnosis. Preoperative diagnoses included LCDIIIA/A546T (1 eye), R124 l+DT125-DE126 (4 eyes), GICD/R555W (14 eyes), LCDI/R124C (6 eyes), SGD/R124 l (16 eyes), and CDBII/R555Q (1 eye). INTERVENTION: Two excimer lasers (Summit Excimed UV 200, Summit Technology, Waltham, MA and Nidek EC 5000, Nidek, Inc., Gamagori, Japan) were used to perform all PTKs. Indications for performing PTK after a graft were severe decrease of the best-corrected visual acuity (BCVA) related to recurrent corneal deposits and/or painful recurrent epithelial erosions. MAIN OUTCOME MEASURES: Preoperative and postoperative BCVA were analyzed, significant recurrences after treatment were noted, and postoperative complications were recorded. RESULTS: Mean preoperative BCVA was 0.2 +/- 0.12 in the decimal chart, mean postoperative BCVA was 0.52 +/- 0.16 with a mean follow-up of 3.13 +/- 1.77 years (range, 0.3-6.65 years). Visual acuity was significantly improved after surgery (P < 0.05). The magnitude of the change in visual acuity was dependent on the mutation (P < 0.001). Seven symptomatic recurrences were observed. One regressive graft rejection and 4 cases of severe postoperative haze were observed. No other complications were noted. CONCLUSIONS: PTK is a simple, safe, and efficient technique for the treatment of recurrent corneal dystrophies; in many cases it prevents or delays the major incumbent problems of repeated grafting.

Adult↗
PubMed2003

Hereditary cerebral hemorrhage with amyloidosis Dutch type (AbetaPP 693): decreased plasma amyloid-beta 42 concentration.

Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is a rare autosomal dominant disorder caused by an amyloid-beta precursor protein (AbetaPP) 693 mutation that clinically leads to recurrent hemorrhagic strokes and dementia. The disease is pathologically characterised by the deposition of Abeta in cerebral blood vessels and as plaques in the brain parenchyma. This study measured the Abeta40 and Abeta42 concentration in plasma of Dutch AbetaPP693 mutation carriers and controls. We found that the Abeta40 concentration was not different between AbetaPP693 mutation carriers and controls. However, the Abeta42 concentration was significantly decreased in the mutation carriers. No correlation exists between the APOE(epsilon)4 allele and the plasma of Abeta40 and Abeta42 levels in HCHWA-D patients. This finding contrasted with the increased concentrations found in Alzheimer's disease. Therefore it is suggested that the Dutch AbetaPP693 mutation located within the Abeta coding region of the AbetaPP gene has a different effect not only on clinical and pathological expression but also on Abeta processing.

Adult↗
PubMed2005

Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors.

Restrictive dermopathy (RD) is characterized by intrauterine growth retardation, tight and rigid skin with prominent superficial vessels, bone mineralization defects, dysplastic clavicles, arthrogryposis and early neonatal death. In two patients affected with RD, we recently reported two different heterozygous splicing mutations in the LMNA gene, leading to the production and accumulation of truncated Prelamin A. In other patients, a single nucleotide insertion was identified in ZMPSTE24. This variation is located in a homopolymeric repeat of thymines and introduces a premature termination codon. ZMPSTE24 encodes an endoprotease essential for the post-translational cleavage of the Lamin A precursor and the production of mature Lamin A. However, the autosomal recessive inheritance of RD suggested that a further molecular defect was present either in the second ZMPSTE24 allele or in another gene involved in Lamin A processing. Here, we report new findings in RD linked to ZMPSTE24 mutations. Ten RD patients were analyzed including seven from a previous series and three novel patients. All were found to be either homozygous or compound heterozygous for ZMPSTE24 mutations. We report three novel 'null' mutations as well as the recurrent thymine insertion. In all cases, we find a complete absence of both ZMPSTE24 and mature Lamin A associated with Prelamin A accumulation. Thus, RD is either a primary or a secondary laminopathy, caused by dominant de novo LMNA mutations or, more frequently, recessive null ZMPSTE24 mutations, most of which lie in a mutation hotspot within exon 9. The accumulation of truncated or normal length Prelamin A is, therefore, a shared pathophysiological feature in recessive and dominant RD. These findings have an important impact on our knowledge of the pathophysiology in Progeria and related disorders and will help direct the development of therapeutic approaches.

Abnormalities, Multiple↗
PubMed2004

Prevention of hepatitis B virus recurrence after living donor liver transplantation.

The emergence of lamivudine-resistant hepatitis B mutations is a major complication during pretransplantation treatment. The proper time to begin Lamivudine before transplantation is not yet known. Twenty-six patients received preoperative lamivudine treatment followed by combined lamivudine and hepatitis B immunoglobulin after transplantation up to December 2002. The length of preoperative lamivudine treatment ranged from 13 to 200 days (mean, 52 +/- 37 days). Hepatitis B virus-DNA was positive in 22 of 26 (84.6%) patients before preoperative lamivudine prophylaxis and persistently positive among only 4 of 22 patients (18%) who at transplantation did not show a viral mutation. In all patients, hepatitis B virus-DNA became negative immediately after transplantation. At a median follow-up of 34 months, neither a hepatitis B recurrence nor a mutation had occurred in any patient. The ability to schedule the proper time for preoperative lamivudine prophylaxis is an advantage of living donor liver transplantation.

Antiviral Agents↗
PubMed2003

The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children.

We reviewed the literature to analyze the risk of recurrence of hemolytic uremic syndrome (HUS) after renal transplantation in children. Among 118 children transplanted after post-diarrheal (D+) HUS, 1 (0.8%) had recurrence with graft loss. Among 63 children transplanted after HUS not associated with a prodrome of diarrhea (D-) of unknown mechanism, 13 (21%) had recurrence with graft loss. Of 11 patients with HUS associated with factor H deficiency who were transplanted, 5 lost the graft because of recurrence. Of 7 patients with HUS associated with normal factor H concentration but mutations in factor H gene who were transplanted, probably 2 had recurrence. Three patients with HUS associated with low serum C3, but no factor H deficiency or mutation lost their graft because of recurrence. The risk of recurrence in the autosomal recessive forms of HUS of unknown mechanism is not documented in children, but is around 60% in adults. A similar risk has been reported in the autosomal dominant forms. The only transplant patient with a constitutional deficiency of von Willebrand factor-cleaving protease had recurrence. Further efforts to document the post-transplant course of patients with D- HUS and progress in the understanding of the mechanisms and genetics of the disease are needed to allow more accurate prediction of the recurrence risk and to define therapeutic approaches.

ADAM Proteins↗
PubMed2005

Analysis of genetic events in 17p13 and 9p21 regions supports predominant monoclonal origin of multifocal and recurrent bladder cancer.

Clonality was tested in 86 tumours from 25 patients with recurrent and multifocal superficial bladder transitional cell carcinomas (TCCs) using the analysis of TP53 mutations and of LOH in the 17p13 and 9p21 regions. Tumours from the majority of individuals showed either absence or presence of the same TP53 mutation and/or an identical LOH pattern, with the same allele lost in all tumours. Only two pairs of tumours from two patients had discordant findings, which were incompatible with monoclonality. Therefore, our results rather support the monoclonal model of development of highly recurrent superficial bladder TCCs.

Aged↗