Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers

"Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM"Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-kB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P< .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL.This work was supported by grants from Instituto de Salud Carlos III, from Ministerio de Economía, Industria y Competitividad, Asociación Española Contra el Cáncer (AECC), ComunidadAutónoma de Madrid and Centre for Biomedical Network Research on Cancer (CIBERONC): SAF2013-47416-R, CIBERONC-ISCIII (CB16/12/00291), ISCIII-MINECO-AES-FEDER (Plan Estatal I+D+I 2013-2016), AECC PROYE18054PIRI, CAM B2017/BMD-3778, PIC97/2017_FJD, PIE15/0081, PIE16/01294, and PI19/00715. R.A.-A. is the recipient of PFIS predoctoral fellowship. L.T.-R. is funded by Marie Skłodowska- Curie Individual Fellowship (No 882597). M.R. is supported by CIBERONC (CB16/12/00291) P.M. has a Miguel Servet contract funded by the ISCIII (CP16/00116). L.d.l.F. was supported by the ISCIII contract CA18/00017

Overlap at the molecular and immunohistochemical levels between angioimmunoblastic T-cell lymphoma and a subgroup of peripheral T-cell lymphomas without specific morphological features

The overlap of morphology and immunophenotype between angioimmunoblastic T-cell lymphoma (AITL) and other nodal peripheral T-cell lymphomas (n-PTCLs) is a matter of current interest whose clinical relevance and pathogenic background have not been fully established. We studied a series of 98 n-PTCL samples (comprising 57 AITL and 41 PTCL-NOS) with five TFH antibodies (CD10, BCL-6, PD-1, CXCL13, ICOS), looked for mutations in five of the genes most frequently mutated in AITL (TET2, DNMT3A, IDH2, RHOA and PLCG1) using the Next-Generation-Sequencing Ion Torrent platform, and measured the correlations of these characteristics with morphology and clinical features. The percentage of mutations in the RHOA and TET2 genes was similar (23.5% of cases). PLCG1 was mutated in 14.3%, IDH2 in 11.2% and DNMT3A in 7.1% of cases, respectively. In the complete series, mutations in RHOA gene were associated with the presence of mutations in IDH2, TET2 and DNMT3A (p < 0.001, p = 0.043, and p = 0.029, respectively). Fourteen cases featured RHOA mutations without TET2 mutations. A close relationship was found between the presence of these mutations and a TFH-phenotype in AITL and PTCL-NOS patients. Interestingly, BCL-6 expression was the only TFH marker differentially expressed between AITL and PTCL-NOS cases. There were many fewer mutated cases than there were cases with a TFH phenotype. Overall, these data suggest alternative ways by which neoplastic T-cells overexpress these proteins. On the other hand, no clinical or survival differences were found between any of the recognized subgroups of patients with respect to their immunohistochemistry or mutational profile.This work was supported by grants from the Instituto de Salud Carlos III, from the Ministerio de Economía, Industria y Competitividad (RTICC RD06/0020/0107, RD12/0036/0060, PI 12/1682, PT13/0010/0007, PI16/ 01294, SAF2013-47416-R, CIBERONC-ISCIII, PIE15/ 0081, ISCIII-MINECO AES-FEDER (Plan Estatal I+D+I 2013–2016): PI14/00221, PIE14/0064, PIE15/0081 and PIE16/01294)) and the Asociación Española Contra el Cáncer, Spain. JG-R is a recipient of an iPFIS predoctoral fellowship (IFI14/00003) from ISCIII-MINECO-AESFEDER (Plan Estatal I+D+I 2013–2016). MSB was supported by a Miguel Servet contract (CP11/00018) from the ISCIII-MINECO-AES-FEDER (Plan Nacional I+D+I 2008–2011), and currently holds a Miguel Servet II contract (CPII16/00024), supported by ISCIII-MINECOAES- FEDER (Plan Estatal I+D+I 2013–2016) and the Fundación de Investigación Biomédica Puerta de Hierro.S

DUSP22-rearranged anaplastic lymphomas are characterized by specific morphological features and a lack of cytotoxic and JAK/STAT surrogate markers

This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Economy and Competence (MINECO, RTICC ISCIII and CIBERONC) (SAF2013-47416- R, RD06/0020/0107-RD012/0036/0060 and Plan Nacional I+D+I: PI16/01294 and PIE15/0081), AECC and the Madrid Autonomous Community

Diagnostic problem of malformed infants born from diabetic mothers

Epidemiología y Teratología: Resultados de estudios sobre los datos del ECEMCTaking into consideration that teratogenic agents do not alter the 100% of exposed pregnancies, we posit that each malformed infant born from a diabetic mother should no be automatically consider as having a diabetic embryofetopathy without a deep evaluation of other potential causal agents. The diagnosis of malformed infants whose mothers were diabetic is not always easy. For instance, if the child only have a cardiac defect, this may be due to maternal diabetes, but also to a big amount of other agents either genetics or environmental. In order to facilitate the diagnosis of infants born of diabetic mothers, we calculated and analyzed the concepts of frequency and specificity. To do this, we used the 33,076 malformed infants of the ECEMC (Spanish Collaborative Study of Congenital Malformations) database. Once we excluded 4,069 cases who had well known syndromes, 759 cases because their mothers had gestational diabetic, and 1,006 with not specification of the diabetic status of their mothers, we get 27,242 malformed infants for the present study. This group was divided in three study groups: the first one was made up with the 38 infants diagnoses as having a diabetic embryofetopathy. The second group included 64 malformed infants whose mothers were diabetics but they were not considered as having a diabetic embryofetopathy. Finally, the third group included the rest of 27,140 malformed infants whose mother had not diabetes mellitus or gestational diabetes. For the study we selected the defects and group of defects included in Table 1. We calculated the relative frequency (FR), by dividing the percentage of each of the studied congenital malformations in the two groups of infants whose mothers were diabetic, by the percentage of the same malformation in the group of infants born of non diabetic mothers. Obviously, all the studied defects, but hypospadias, nevus/angiomas, and digestive atresias (which were included as controls, since they are not considered part of the diabetic embryofetopathy), have to be significantly more frequent in the first group, because the infants were diagnosed based in the presence of these defects in their patterns. But this group permit to understand the concepts of frequency and specificity. In fact, Table 1 shows that while the most frequent defect in this consecutive series of infant born with diabetic embryofetopathy, correspond to vertebral anomalies (44.74%), followed by cardiovascular defects (39.47%), the most specific is sacral agenesis/hypoplasia, because it frequency in this group is 131.56 times higher than in the group of infants of non diabetic mothers. In this table, it is also shows that in the group of malformed infants whose mothers were diabetics, some of them may have diabetic embriofetopathy, but were not diagnoses because the lack of some type of information (such as karyotypes, family history, prenatal exposure to others potential related factors, among others). We discussed the importance of performing the diagnosis of malformed infants born to diabetic mothers taking into consideration that among this group of mothers, we can also observed malformed infants with different type of yndromes that in many cases are clinically indistinguishable from the diabetic embryofetopathy (i.e. Jarcho-Levin or Casamassima syndromes, chromosomal abnormalities...), or with isolated malformations (i.e. cardiovascular), that may, or may not, be related with the maternal diabetes. All these consideration are important, not only because the recurrence risk could be much higher than that of the maternal diabetes, but also because the secular increasing trend in diabetic mothers due to the life style.N

La vacuna de la rubéola y el embarazo

TeratologíaRubella is a viral infection that when it occurs during pregnancy, especially during the first trimester, could cause congenital rubella embryophaty (CRE) with devastating consequences for the developing embryo and fetus. CRE includes serious birth defects such as: cataracts, deafness and heart disease, among others. However the frequency of CRE has decreased dramatically since the general use of rubella vaccine. The immigrant population in Spain constitutes a group of concern for rubella infection among other infectious diseases due to the lack of previous vaccination in many individuals. Thus, a vaccination programme towards immigrants, specially all young women should be considered. Pregnant women should not be vaccinated, and women who are not pregnant should avoid conceiving for at least 28 days following vaccination. However if a vaccination occurs during pregnancy, the potential risk is only theoretical and a tranquilizer counseling should be performed together with a high resolution ecography.N

Resultados de la actividad de los Servicios de Información Telefónica sobre Teratógenos (SITTE y SITE) durante el año 2004 y análisis del nivel cultural de la población usuaria

Resultados de otras actividades del ECEMCWe present a summary of the activity of the two teratology information services: SITTE (for health professional) and SITE (for the general population), during 2004. A total of 6.407 calls were received, 1.456 of them were made by health professional and the remaining 4.951 by the general population. Drugs were, one more year, the most common question in either services, specially drugs affecting CNS. We also analyzed the cultural level of the women that used the SITE during the last ten years. The results show that most of the users of the service belong to the higher cultural levels, measured by the level of their educational studies. We conclude that is necessary to consider new strategies particularly aimed to reach to those women with low level of education (or low cultural level).N

Motivation, optimism and self-concept in sports

Tres constructos psicológicos como son autoconcepto físico, optimismo y motivación podrían estar más relacionados en el ámbito del deporte de lo que parece a priori. El objeto de este estudio es analizar cómo se relacionan estas variables. Se espera que se revelen algunas correlaciones positivas entre los distintos constructos y su relación con ambos géneros. Para ver la relación entre las tres variables se contó con una muestra de 113 participantes (51 mujeres y 62 hombres), de edades comprendidas entre 18 y 60 años. Los resultados obtenidos mostraron la relación entre autoconcepto físico y optimismo, y optimismo y motivación sin diferencias entre hombres y mujeres. Sin embargo también se ha encontrado una relación negativa entre autoconcepto y motivación, contraria a lo que cabría esperar. Tres constructos psicológicos como son autoconcepto físico, optimismo y motivación podrían estar más relacionados en el ámbito del deporte de lo que parece a priori.Three psychological constructs such as the physical self, optimism and motivation may be more related to the field of sport than it seems a priori. The purpose of this study is to analyze how these variables are related. It is expected that some positive correlations between constructs and their relationship with both genders are revealed. To see the relationship between the three variables had a sample of 113 participants (51 women and 62 men), aged between 18 and 60. The results showed the relationship between physical self and optimism, and optimism and motivation no difference between men and women. However it has also found a negative relationship between self -concept and motivation, contrary to what one would expect.ReiDoCrea. Departamento de Psicología Social. Universidad de Granada

The Activity of the Spanish Teratology Information Services (SITTE and SITE) during 2008

Otros Resultados: Actividad TraslacionalWe summarize the activity of the two Teratology Information Services: SITTE (for health professionals) and SITE (for the general population), during 2008. The total number of calls received in both services was 4,910 (943 from SITTE and 3,967 from SITE). This number has increased compared to previous year. The main users of the SITTE (gynecologists 54.96%) and the SITE (pregnant women 79.89%), have asked preponderantly about the use of drugs (70.22% of the SITTE and 37.49% of the SITE phone calls), during ongoing pregnancies at the moment they were calling (82.82% in the SITTE and 85.18% in the SITE). Additionally, we analyze the type of consulted factors and some characteristics of the users to orientate our work more effectively to the actual demand.N

Resultados de las llamadas recibidas por el Servicio de Información Telefonica sobre Teratogenos Español (SITTE) y por el Servicio de Informacion Telefónica para la Embarazada (SITE) durante el año 2002

Resultados de otras actividades del ECEMCWe present the results of the Spanish Teratology Information Services (SITTE addressed to health professionals and SITE addressed to the general population) during 2002. The total number of calls received in both services was 5,587 (1,416 of them by the SITTE and 4,171 by the SITE). As in the last years, the most frequent enquiry in both services was the drugs exposure during pregnancy. However, we would like to point out that questions on environmental and working chemicals products are increasing. Probably this is so because of a higher concern in this area on primary prevention of congenital malformations.N