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Here we describe the clinical, microbiological, epidemiological, and molecular characterization of an outbreak of multidrug-resistant Acinetobacter baumannii (MRAB) involving 5 patients admitted to the internal medicine ward of our hospital. Over a 6-week period, 5 MRAB isolates were recovered from 5 patients, including 1 with fatal meningitis, 3 with skin and soft tissue infections, and 1 with respiratory colonization. One sample obtained during environmental monitoring in the ward was A. baumannii-positive. According to the pulsed-field gel electrophoresis typing results, the strains isolated from all patients and the environmental sample belonged to a single clone, identified as ST79 by multilocus sequence typing. The blaOXA-24 and blaOXA-51 carbapenemases were detected in all isolates. Four patients died, but only the death of the meningitis patient was probably related to the A. baumannii infection. The infection source was probably the hands of the healthcare workers because the outbreak strain was isolated from the surface of a serum container. The results of the present study revealed the importance of strict adherence to control measures by all healthcare workers because the consequences of noncompliance can be very serious.

Conventional renal cell carcinoma (CRCC) may appear in families with germline translocations involving chromosome 3, although a recurrent responsible gene has not been found. We recently described a family with CRCC and a constitutional t(3;8)(p14.1;q24.23), and we demonstrated that no genes were disrupted by the translocation breakpoints. In order to investigate the genetic origin and features of the CRCC tumors that occurred in this family, we have extended the pedigree up to four generations, and analyzed peripheral blood samples from 36 members, CRCC tumors, normal renal tissues, and a gastric tumor. (1) By means of comparative genomic hybridization (CGH), we have detected loss of the derivative chromosome carrying 3p in all CRCC but not in the corresponding normal renal tissue. In addition, by means of the fluorescence in situ hybridization technique, we have observed that not all tumoral cells lose the der(3p), which suggests that, previous to this loss, another hit should occur to initiate the transformation of normal into tumoral cells. (2) All known mechanisms of inactivation of the candidate von Hippel-Lindau (VHL) gene have been studied in the tumors, detecting alterations in 65% of them. This confirms that inactivation of the VHL gene is not always required to develop CRCC, and that (an)other suppressor gene(s) on 3p could be involved. (3) We discard FHIT as an alternative pathway to VHL. We have not found new candidate regions along 3p by using a 1-Mb resolution array-based CGH. (4) The tumorigenesis mechanism of a second gastric tumor developed in the probandus is different from that of CRCC.

An alternative model has been proposed for the development of clear-cell renal cell carcinoma (RCC) in families where chromosome 3 translocations segregate with the disease. In this model, the existence of a translocation involving chromosome 3 would favour the non-disjunctional loss of the derivative chromosome carrying the 3p segment. Additionally, subsequent somatic mutations in the VLH gene, located in 3p25-26, would inactivate this tumour suppressor gene. In the present work, we describe a new family with two clear-cell RCC affected members and a t(3;8)(p13;q24.1) translocation in two consecutive generations. We observed loss of the derivative chromosome carrying the 3p segment (der(8)) and somatic mutation of the VHL gene in the left-kidney tumoral tissue of the proband. His right-kidney tumour carried a different VHL mutation and loss of heterozygosity (LOH) was not detected. The mother of the proband was also clear-cell RCC-affected but the tumoral tissue analysed did not carry any VHL gene mutations. Another member of the family, a maternal aunt, had a papillary RCC and did not carry this translocation, the LOH on 3p or the VHL somatic mutations. Haplotype analysis of the three affected members revealed that they did not inherit a common region on 3p, confirming the different genetic origin of both tumour types. Finally, the presence of RCC in other non-available members of the family highlights the overall risk for RCC in families with chromosome 3 translocations. In the present work, we have confirmed the proposed mechanism for the development of clear-cell RCC in this family, although we cannot discard the existence of other genes, in addition to VHL, being involved in hereditary RCC.