FGFR1 Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer.

post-print262 K

Natación artística en niñas: antropometría, genotipo y rendimiento deportivo.

En cada deporte es importante optimizar peso y composición corporal y la genética y los datos antropométricos pueden influir en rendimiento deportivo y salud, sobre todo en deportistas menores. Este estudio analiza 60 nadadoras artísticas entre 9 y 17 años, divididas en tres grupos de edad: ≤12, 13-15 y 16-17 años. Se realizó un análisis de medidas antropométricas, edad de menarquia, genotipo relacionado con rendimiento (gen ACTN3) y resultados deportivos, con objetivo de relacionar estos parámetros entre sí en los grupos de edad. Las nadadoras de mayor edad mostraron tendencia a portar el genotipo heterocigoto RX de ACTN3. En este estudio, la práctica de este deporte podría tener impacto en índice de masa corporal, pliegue tricipital, peso y edad de menarquia. La mayor prevalencia del genotipo heterocigoto ACTN3 R577X podría ofrecer una ventaja, pero el rendimiento en competición de las nadadoras artísticas tuvo poca relación con sus medidas antropométricas.post-print680 K

FGFR1 Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer

HER2-positive breast cancer (BC) is an aggressive subtype that affects 20–25% of BC patients. For these patients, neoadjuvant therapy is a good option that targets a pathological complete response (pCR) and more breast-conserving surgery. In effect, the outcomes of patients with HER2-positive BC have dramatically improved since the introduction of anti-HER2 antibodies such as trastuzumab (TZ) and/or pertuzumab (PZ) added to chemotherapy. This study sought to examine whether correlation exists between copy number variations (CNVs) in several genes related to the PI3K/AKT pathway (HER2, FGFR1, PIK3CA, AKT3 and MDM2) and the efficacy of anti-HER2 neoadjuvant treatment in patients with early HER2-positive BC. Forty-nine patients received TZ or PZ/TZ and chemotherapy as neoadjuvant treatment. Gene CNVs were determined by quantitative polymerase chain reaction on paraffin-embedded biopsy specimens. The response to 6 months of therapy was assessed by Miller–Payne grading of the tumor on surgical resection; grades 4 and 5, indicating >90% tumor reduction, were defined as a good response. A good response was shown by 64.5% and a pCR by 31.2% of patients. When stratified by anti-HER2 antibody received and gene CNV, it was found that patients with FGFR1 gene amplification or those with FGFR1 amplification treated with TZ alone showed a poor response (p = 0.024 and p = 0.037, respectively). In the subset of patients treated with TZ/PZ combined, the pCR rate was significantly lower among those showing FGFR1 amplification (p = 0.021). Although based on a small sample size, our findings suggest that patients with FGFR1 amplification might benefit less from anti-HER2 antibody therapy

Genetic Variants of ANGPT1, CD39, FGF2 and MMP9 Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer

Angiogenesis pathway genes show substantial genetic variability causing inter-individual differences in responses to anti-angiogenic drugs. We examined 20 single nucleotide polymorphisms (SNPs) in 13 of these genes to predict tumour response and clinical outcome measured as progression free survival (PFS) and overall survival (OS) in 57 patients with metastatic colorectal cancer (mCRC) given bevacizumab plus chemotherapy. SNPs were detected (iPLEX® Assay) in genomic DNA extracted from formalin-fixed paraffin-embedded tumour specimens. The variant allele CD39 rs11188513 was associated with a good tumour response (p = 0.024). Patients homozygous for the wild-type allele FGF2 rs1960669 showed a median PFS of 10.95 months versus 5.44 months for those with at least one variant allele-A (HR 3.30; 95% CI: 1.52–7.14; p = 0.001). Patients homozygous for wild-type MMP9 rs2236416 and rs2274755 showed a median PFS of 9.48 months versus 6 and 6.62 months, respectively, for those with at least one variant allele (p = 0.022, p = 0.043, respectively). OS was also lengthened to 30.92 months (p = 0.034) in carriers of wild-type ANGPT1 rs2445365 versus 22.07 months for those carrying at least one variant allele-A. These gene variants were able to predict clinical outcome and tumour response in mCRC patients given bevacizumab-based therapy

Diversidad genética en poblaciones del centro de Marruecos y sur de España : análisis de poliforfismos STRs autosómicos y del cromosoma Y

Tesis inédita presentada en la Universidad Europea de Madrid. Facultad de Ciencias Biomédicas. Programa de Doctorado en Biomedicina Ciencias de la SaludLa variabilidad genética en el ADN repetido está siendo ampliamente estudiada en poblaciones humanas de diferente origen geográfico y étnico. La importancia de estos estudios es doble: por un lado, como herramienta en el ámbito forense para la identificación de individuos y, por otro, para el establecimiento de relaciones genéticas entre poblaciones humanas histórica o geográficamente relacionadas. En el presente trabajo se han analizado 15 polimorfismos STR autosómicos y 16 polimorfismos STR presentes en el cromosoma Y, en una población española de origen andaluz procedente de La Alpujarra y dos marroquíes, una de origen árabe y otra de origen bereber. Los resultados han sido comparados con información obtenida por otros autores en otros grupos humanos, con el fin de aportar más datos en el estudio de la antigüedad de las relaciones genéticas entre el Norte de África y el Sur de Europa. Los resultados obtenidos muestran que las tres poblaciones estudiadas se encuentran dentro del rango de variación de las poblaciones de la zona del Mediterráneo Occidental, quedando englobadas dentro del grupo de afinidades genéticas europeo o norteafricano, según su origen. Del mismo modo, se ha profundizado en la estructura genética de las poblaciones del Norte de África analizada a partir de cálculos AMOVA y se ha podido constatar la falta de un patrón claro de agrupamiento entre las poblaciones del Norte de África, ya sea siguiendo criterios geográficos o bien criterios lingüísticos. El presente estudio pretende, además, contribuir a completar las bases de datos online existentes en Internet y creadas con el fin de ser usadas como referencia en estudios genealógicos y forenses, para poder estudiar la distribución de estos marcadores genéticos a nivel mundial y conocer mejor las relaciones entre las poblaciones humanas actuales. [Resumen Teseo

Genetic differences among North African Berber and Arab-speaking populations revealed by Y-STR diversity

Y-chromosome STR polymorphisms are inherited in a haploid state which makes them a powerful tool for easy tracing of paternal lineage and for use in human population evolutionary studies. North-African Y chromosomal diversity has traditionally been studied in order to find genetic and geographic associations as well as to test how natural and cultural barriers have affected the degree of genetic flow not only within North Africa but also in a wider Mediterranean context. The degree of Berber/Arab genetic differentiation in the Moroccan population has been tested for a complete set of forensic markers as sixteen Y-chromosomal short tandem repeats (STRs) (DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and GATA H4.1). The results suggest considerable population heterogeneity in North Africa.1.975 JCR (2011) Q2, 28/85 Biology, 61/158 Public, environmental & occupational healt

Usefulness of autosomal STR polymorphisms beyond forensic purposes: data on Arabic- and Berber-speaking populations from central Morocco

BACKGROUND: This work describes, for the first time, the profile of Middle Atlas Berbers and Arabic-speaking central Moroccans for 15 autosomal STR loci widely used in forensic sciences. AIM: The main objectives were to determine the degree of heterogeneity among different Moroccan samples to identify geographic or linguistic patterns and to evaluate the usefulness of forensic STRs in anthropological studies. SUBJECTS AND METHODS: Blood samples were collected from 71 Arabic-speakers and 75 Berbers from the regions of Doukkala (central-west coast) and Khenifra (Middle Atlas), respectively. The AmpFlSTR Identifier kit was used to genotype 15 autosomal STR in both samples. RESULTS: Middle Atlas Berbers showed slightly higher genetic variation values compared to Arabic-speakers, both in the number of alleles and heterozygosity. In order to assess population relationships, data from Morocco, Algeria, Tunisia, Libya, Egypt, Kuwait, Qatar, Palestine, Syria, South-Spain and Turkey were included in the analysis. Within Morocco, genetic distances followed a clear geographic pattern. In the Arabic-speaking sample the genetic proportion of 'Arabian' admixture was estimated in 13%. CONCLUSION: The low value of admixture suggests that the Arabization of Morocco had a reduced demographic impact, which should be taken with caution because it is based on autosomal STRs with low inter-population variation levels.1.484 JCR (2012) Q2 40/83 Biology; Q3, 86/158 Public, environmental & occupational healt

Pharmacogenetics of ugt genes in North African populations

UEM39 20163.503 JCR (2018) Q2, 57/174 Genetics & Heredity, 73/267 Pharmacology & Pharmacy1.096 SJR (2018) Q1, 71/335 Pharmacology; Q2, 63/177 Molecular Medicine, 140/351 GeneticsNo data IDR 2018UE

Transversalidad en los estudios superiores de Óptica y Optometría y Ciencias Ambientales

SIN FINANCIACIÓNNo data 2006UE

Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer

In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.Sin financiación4.375 JCR (2020) Q2, 115/242 Oncology1.228 SJR (2020) Q2, 110/354 OncologyNo data IDR 2020UE