Keratinocytic epidermal nevi are associated with mosaic RAS mutations.

BACKGROUND: Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations. METHODS: This study screened 72 KEN for activating mutations in RAS genes and other oncogenes. RESULTS: Activating RAS mutations were identified in 28/72 (39%) of KEN. HRAS was the most commonly affected oncogene (86%), with the HRAS p.G13R substitution representing a new hotspot mutation. CONCLUSION: These results indicate that activating RAS somatic mutations leading to mosaicism result in benign KEN of the skin. Given the prevalence of KEN, mosaic HRAS mutations appear to be more common in patients than germline ones. These findings identify KEN as a mosaic RASopathy and lend further support to the notion that genetic mosaicism is an important contributor to disease.

STRs data for the loci D3S1385, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820 from Córdoba (Argentina).

Allele and genotype frequencies for nine STRs loci included in the AmpFlSTR Profiler Plus kit (D3S1385, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820), were determined from urban and countryside population of Córdoba (Argentina). All loci meet the Hardy-Weinberg expectation, and there is little evidence for alleles association between these nine loci. The results demonstrate that these loci can be useful for databasing purposes in human identification and parentage testing in the population of Córdoba (Argentina).

Allele frequencies and statistical parameters for Penta E and Penta D STR loci in Córdoba (Argentina) population.

POPULATION: Urban and countryside population of Córdoba (Argentina).

ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors.

Urothelial bladder cancer (UBC) is heterogeneous at the clinical, pathological, genetic, and epigenetic levels. Exome sequencing has identified ARID1A as a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in UBC. Here, we assess ARID1A alterations in two series of patients with UBC. In the first tumor series, we analyze exons 2-20 in 52 primary UBC and find that all mutant tumors belong to the aggressive UBC phenotype (high grade non-muscle invasive and muscle invasive tumors) (P = 0.05). In a second series (n = 84), we assess ARID1A expression using immunohistochemistry, a surrogate for mutation analysis, and find that loss of expression increases with higher stage/grade, it is inversely associated with FGFR3 overexpression (P = 0.03) but it is not correlated with p53 overexpression (P = 0.30). We also analyzed the expression of cytokeratins in the same set of tumor and find, using unsupervised clustering, that tumors with ARID1A loss of expression are generally KRT5/6-low. In this patient series, loss of ARID1A expression is also associated with worse prognosis, likely reflecting the higher prevalence of losses found in tumors of higher stage and grade. The independent findings in these two sets of patients strongly support the notion that ARID1A inactivation is a key player in bladder carcinogenesis occurring predominantly in FGFR3 wild type tumors.

Nephrocystin-1 forms a complex with polycystin-1 via a polyproline motif/SH3 domain interaction and regulates the apoptotic response in mammals.

Mutations in PKD1, the gene encoding for the receptor Polycystin-1 (PC-1), cause autosomal dominant polycystic kidney disease (ADPKD). The cytoplasmic C-terminus of PC-1 contains a coiled-coil domain that mediates an interaction with the PKD2 gene product, Polycystin-2 (PC-2). Here we identify a novel domain in the PC-1 C-terminal tail, a polyproline motif mediating an interaction with Src homology domain 3 (SH3). A screen for interactions using the PC-1 C-terminal tail identified the SH3 domain of nephrocystin-1 (NPHP1) as a potential binding partner of PC-1. NPHP1 is the product of a gene that is mutated in a different form of renal cystic disease, nephronophthisis (NPHP). We show that in vitro pull-down assays and NMR structural studies confirmed the interaction between the PC-1 polyproline motif and the NPHP1 SH3 domain. Furthermore, the two full-length proteins interact through these domains; using a recently generated model system allowing us to track endogenous PC-1, we confirm the interaction between the endogenous proteins. Finally, we show that NPHP1 trafficking to cilia does not require PC-1 and that PC-1 may require NPHP1 to regulate resistance to apoptosis, but not to regulate cell cycle progression. In line with this, we find high levels of apoptosis in renal specimens of NPHP patients. Our data uncover a link between two different ciliopathies, ADPKD and NPHP, supporting the notion that common pathogenetic defects, possibly involving de-regulated apoptosis, underlie renal cyst formation.

Duplicación apendicular / Appendicular duplication

El apéndice cecal es un órgano pródigamente estudiado, debido a la gran frecuencia con que se producen inflamaciones agudas en él, no obstante, son menos conocidas las anomalías congénitas que resultan en una duplicación apendicular, por ser esta una entidad rara. Se presenta un caso de una paciente que se interviene quirúrgicamente por una apendicitis aguda, en la cual se encontró otro apéndice cecal. Se realiza discusión y revisión del tema(AU)

Cecal appendix is much studied organ due to the high frequency of its acute inflammations, however, the congenital anomalies are less associated resulting in a appendicular duplication because of it is a rare entity. This is the case of a female patient operated on due to acute appendicitis founding another cecal appendix(AU)

Técnica de Mohan P: desarda en la Herniografía Inguinal de forma ambulatoria / Mohan P: desarda’s technique in ambulatory inguinal herniorraphy

Se describe en este trabajo nuestra experiencia con una técnica de reparación de la hernia inguinal, en la cual la pared posterior del canal inguinal se fortalece con una franja fija de la aponeurosis del músculo Oblicuo Externo para producir una pared posterior fuerte y fisiológicamente activa. Revisamos las historias clínicas de los primeros 250 pacientes operados por esta técnica, que incluyen los meses de septiembre del 2001 a diciembre del 2005, los cuales son seguidos por consulta externa en nuestro Centro. Todos los pacientes fueron operados de forma ambulatoria. La hernia inguinal derecha y la variedad indirecta fue la más frecuente, hubo dos pacientes que presentaron sepsis de la herida y un paciente tuvo una recidiva. El ahorro económico fue significativo. La técnica quirúrgica es fácil de realizar, no requiere prótesis y ofrece resultados equivalentes a las reportadas que utilizan malla.

The objective of this work is to show our experience with an inguinal hernia repair technique in which the posterior wall of the inguinal chanel is streighten by an strip of the External Oblique Aponeurosis to make a hard and physiological active posterior wall. We present a series of the first 250 patients who underwent surgery by this technique between September 2001 to December 2005, all of them were follow up in outpatient department in our hospital. All of them were operated on ambulatory regimen. The right indirect inguinal hernia was the most frecuent. Two patients showed wound infection and one had an early recurrence. This technique isn’t expensive. The technique presented is ease to do, and involves minimal dissection and surgical trauma. It doesn’t need prothesis and show the same results.