Gene aberration profile of tumors of adolescent and young adult females
نویسندگان
چکیده
There has been little improvement in the prognosis for adolescent and young adult (AYA) tumor patients. Hence, there is an urgent need to understand the etiology of tumor development and identify actionable gene aberrations to improve prevention and therapy. Here, 76 sporadic tumors (48 breast, 22 ovarian, and six uterine) from 76 AYA females (age range, 25-39 years) were subjected to whole exome and RNA sequencing to determine their mutational signatures and actionable gene profiles. Two individuals with breast cancer (4.2% of cases) and one with ovarian cancer (5.3% of cases) carried germline BRCA2 mutations. The two cases with breast tumors also each carried an additional deleterious germline mutation: one in TP53 and the other in CHEK2. Mutational signature analysis of the 76 tumors indicated that spontaneous deamination of 5-methylcytosine and activity of the APOBEC cytidine deaminase protein family are major causes of mutagenesis. In addition, 18 breast or ovarian tumors (18/70, 26%), including the three cases with germline BRCA2 mutations, exhibited a predominant "BRCAness" mutational signature, an indicator of functional BRCA1/BRCA2 deficiency. Actionable aberrations and high tumor mutation burdens were detected in 24 breast (50%), 17 ovarian (77%), and five uterine (83%) tumor cases. Thus, mutational processes and aberrant genes in AYA tumors are largely shared with those identified in non-AYA tumors. The efficacy of molecular targeting and immune checkpoint inhibitory therapies should be explored for both AYA and non-AYA patients.
منابع مشابه
Neuroblastoma after Childhood: Prognostic Relevance of Segmental Chromosome Aberrations, ATRX Protein Status, and Immune Cell Infiltration1
Neuroblastoma (NB) is a common malignancy in children but rarely occurs during adolescence or adulthood. This subgroup is characterized by an indolent disease course, almost uniformly fatal, yet little is known about the biologic characteristics. The aim of this study was to identify differential features regarding DNA copy number alterations, α-thalassemia/mental retardation syndrome X-linked ...
متن کاملClinicopathologic and Survival Characteristics of Childhood and Adolescent Brain and Spinal Cord Tumors in Center of Iran
Background: The brain and spinal cord tumors account for 15% to 20% of all childhood malignancies. It is important to know the epidemiologic characteristics and survival of these patients to better understand the disease and the factors affecting its prognosis. The aim pf this study was to characterize the clinicopathology and survival rate of childhood and adolescent brain and spinal cord tumo...
متن کاملCorrelation between adolescent chronic emotional stress and incidence of adult cardiovascular disease in female rats
Objective(s): Association of adolescent emotional stress (ES) with the incidence of cardiovascular disease (CVD) at older age was investigated. Materials and Methods: 21 female rats were divided into three groups of 7 each; ES, foot-shock, and control. Chronic ES was induced by exposing the rats to witness foot-shock of their neighboring...
متن کاملAngular Photogrammetric Analysis of the Soft Tissue Facial Profile and Sexual Dimorphism in Young Adults in Zanjan
Background and Aim: Facial features are different depending on gender and race. These features are usually studied in profile view. Angular evaluation of the facial soft tissue profile is important in males and females of different races for correct diagnosis and treatment planning. For this reason, in the present study, we measured the facial profile angles in young adults in Zanjan. Material...
متن کاملEffects of optimized photorefractive keratectomy (PRK) operation on the asphericity and high-order aberration changes
Background: Optimized is a common and important method in which aberrations are created by the device and the surgeon, but high-grade aberrations are out of the surgeon's control and are induced by the device in the patient. The aim of this study was the evaluation of out-of-control high-order aberration changes before and after PRK surgery and these impact on vision outcome. Materials and meth...
متن کامل