RESUMO
BACKGROUND/AIM: Historically, breast cancer has been treated according to an evaluation of biomarkers, such as the estrogen receptor and HER2 status. Recently, molecular profiling has been used to detect driver mutations and select anti-cancer treatment strategies. In addition to detecting pathogenic mutations, the total mutation count (tumor mutation burden) has been considered as another biomarker. MATERIALS AND METHODS: We performed molecular profiling of 143 breast cancer tissues obtained from resected tissues via surgical operation. RESULTS: Suspected germline mutations were detected in 10% of the patients with a higher somatic mutation ratio. CONCLUSION: As hypermutated breast cancers are more likely to benefit from certain anti-cancer treatment strategies, molecular profiling can be used as a biomarker.
Assuntos
Neoplasias da Mama/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Mutação em Linhagem Germinativa/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores de Estrogênio/genéticaRESUMO
The chromosomal region critical in Down syndrome has long been analyzed through genotype-phenotype correlation studies using data from many patients with partial trisomy 21. Owing to that, a relatively small region of human chromosome 21 (35.9 ~ 38.0 Mb) has been considered as Down syndrome critical region (DSCR). In this study, microarray-based comparative genomic hybridization analysis identified complex rearrangements of chromosome 21 in a patient manifesting clinical features partially overlapped with that of Down syndrome. Although the patient did not show up-slanting palpebral fissures and single transverse palmar creases, other symptoms were consistent with Down syndrome. Rearrangements were analyzed by whole-genome sequencing using Nanopore long-read sequencing. The analysis revealed that chromosome 21 was fragmented into seven segments and reassembled by six connected points. Among 12 breakpoints, 5 are located within the short region and overlapped with repeated segments. The rearrangement resulted in a maximum gain of five copies, but no region showed loss of genomic copy numbers. Breakpoint-junctions showed no homologous region. Based on these findings, chromoanasynthesis was considered as the mechanism. Although the distal 21q22.13 region was not included in the aberrant regions, some of the genes located on the duplicated regions, SOD1, SON, ITSN1, RCAN1, and RUNX1, were considered as possible candidate genes for clinical features of the patient. We discussed the critical region for Down syndrome, with the literature review.
Assuntos
Cromossomos Humanos Par 21/genética , Cromossomos Humanos/genética , Síndrome de Down/genética , Proteínas Adaptadoras de Transporte Vesicular/genética , Aberrações Cromossômicas , Hibridização Genômica Comparativa/métodos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Proteínas de Ligação a DNA/genética , Síndrome de Down/fisiopatologia , Feminino , Dosagem de Genes/genética , Estudos de Associação Genética , Humanos , Hibridização in Situ Fluorescente/métodos , Lactente , Análise em Microsséries/métodos , Antígenos de Histocompatibilidade Menor/genética , Proteínas Musculares/genética , Superóxido Dismutase-1/genética , Sequenciamento Completo do GenomaRESUMO
A female patient presented with developmental delay, distinctive facial features, and congenital anomalies, including a heart defect and premature lambdoid synostosis. The patient showed a paternally inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving the mitogen-activated protein kinase kinase 2 gene (MAP2K2), in which mutations cause the cardio-facio-cutaneous (CFC) syndrome. Reports of patients with overlapping 19p13.3 microdeletions of this region describe similar clinical manifestations including distinctive facial features: prominent forehead, horizontal/down-slanting palpebral fissures, long midface, pointed chin/angular jaw, sparse eyebrows, and underdeveloped cheekbones. Some of these findings overlapped to that of the patients with 16p13.11 microduplications and CFC syndrome. Although craniosynostosis was occasionally observed in patients with dominant-negative mutations in RAS/MAP kinase signaling genes (RASopathies) related to CFC syndrome, it was also reported in two patients with 16p13.11 microduplications. Genetic contributions of both chromosomal aberrations were discussed.
Assuntos
Craniossinostoses/genética , Deficiências do Desenvolvimento/genética , Displasia Ectodérmica/genética , Insuficiência de Crescimento/genética , Cardiopatias Congênitas/genética , MAP Quinase Quinase 2/genética , Anormalidades Múltiplas/genética , Duplicação Cromossômica/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 19/genética , Craniossinostoses/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Fácies , Feminino , Humanos , Lactente , Cariótipo , Mutação , FenótipoRESUMO
Simpson-Golabi-Behmel syndrome is a congenital malformation syndrome associated with mutations in GPC3, which is located in the Xq26 region. Three new loss-of-function mutations and a global X-chromosome rearrangement involving GPC3 were identified. A female sibling of the patient, who presented with a cleft palate and hepatoblastoma, carries the same chromosomal rearrangement and a paradoxical pattern of X-chromosome inactivation. These findings support variable GPC3 alterations, with a possible mechanism in female patients.