Genetic aberrations and their clinical significance in breast and ovarian cancer

Abstract In tumourigenesis, genetic alterations accumulate in the genes responsible for cell growth, proliferation and DNA repair: proto-oncogenes, tumour suppressor and DNA repair genes. Inactivation of tumour suppressor gene function is commonly recognised as a deletion of one of the two alleles; LOH, loss of heterozygosity. In the present study, LOH of several chromosomal regions was studied in both breast and ovarian cancer. LOH for chromosome region 11q was examined in a large breast cancer consortium cohort (N = 988) and in a Finnish ovarian cancer cohort (N = 78), and the clinical significance of these alterations was evaluated. In breast cancer, LOH of the studied markers at 11q23.1, harbouring approximately 2 Mb of DNA, was seen to be associated with shortened cancer-specific survival. Two candidate genes, ATM (the ataxia telangiectasia disorder gene) and DDX10 (a putative RNA helicase gene) map to this chromosomal region. In ovarian cancer, LOH at 11q23.1–q24 was assigned mainly to two chromosomal regions, A and B, which are proximal and distal to 11q23.2–q23.3, respectively. Only the distal B region was seen to be associated with an aggressive disease course. Therefore, it appears that inactivation of the ATM or DDX10 genes is not crucial for determining the outcome of ovarian cancer. The CHK1 gene at 11q24, encoding a protein kinase required for DNA damage checkpoint function, is a putative target gene at the B region. On the basis of the present results, the main TSG in the studied region involved in the progression of breast cancer maps to 11q23.1 and the corresponding gene for ovarian cancer more distally to 11q23.3-q24. In addition, LOH at 3p, 6q, 8p, 11p, 16q and 17p was examined and their role in the genetic evolution of ovarian cancer was evaluated. Of the studied chromosomal regions, LOH at 17p appeared to be an early event and LOH at 16q24.3, 11q23.3/q24 and 11p appear to occur later in the progression of ovarian cancer

Craniofacial asymmetry from one to three years of age:a prospective cohort study with 3D imaging

Abstract Deformational plagiocephaly (DP) is considered a risk factor for facial asymmetry. This cohort-based, prospective, follow-up study used three-dimensional (3D) stereophotogrammetry to assess the development of facial asymmetry in a normal birth cohort and to investigate the impact of DP on facial asymmetry for the age range of one to three years. The study sample consisted of 75 children: 35 girls (47%) and 40 (53%) boys recruited from Oulu University Hospital. A total of 23 (31%) subjects had a history of DP in infancy. 3D facial images were obtained at the mean (SD) age of 1.01 (0.04) year old at T1 and 3.02 (0.14) years old at T2. To determine facial asymmetry, both landmark-based and surface-based facial symmetry methods were used. As measured with the surface-based methods, upper facial symmetry improved from T1 to T2 (p < 0.05). As measured with the landmark-based methods, facial symmetry improved on the upper and lower jaw from T1 to T2 (p < 0.05). The asymmetric effect of DP on the upper parts of the face tends to correct spontaneously during growth. Results indicate that previous DP does not seem to transfer to facial or occlusal asymmetry at the age of three years old

A longitudinal study of facial asymmetry in a normal birth cohort up to 6 years of age and the predisposing factors

Abstract Objectives: This prospective, population-based cohort study aimed to investigate the development of facial asymmetry up to 6 years of age using a three-dimensional (3D) soft tissue imaging method in a normal population. In addition, the study sought to identify potential predisposing factors to facial asymmetry. Methods: A total of 102 newborns were enrolled in the study at birth. 3D stereophotogrammetric images of the head and face were analysed at the ages of 12 months (T1), 3 years (T2), and 6 years (T3). The surface-based analysis involved the calculation of the average distance (mm) and the symmetry percentage (%) between the original and mirrored surfaces. For landmark-based analysis, the distance of facial landmarks to the facial midline was examined. Results: The final analysis included 70 (68.6%) subjects. Surface-based analysis showed a significant improvement of facial symmetry from T1 to T3 in all facial areas. Landmark-based analysis showed that upper facial landmarks were located, on average, slightly on the left and lower facial landmarks slightly on the right in relation to the facial midline (P < 0.001). Limitations: The size of the study population was limited. Facial posture may affect the reliability of the results, especially in younger children. Conclusions: Facial asymmetry is detectable in early childhood and tends to reduce with age in young children. The lower face deviates slightly to the right, and the upper face to the left in relation to the facial midline. Possible predisposing factors for facial asymmetry at the age of 6 years include deformational plagiocephaly, sleeping position, and previous facial asymmetry

A 3D follow-up study of cranial asymmetry from early infancy to toddler age after preterm versus term birth

Abstract Preterm infants are at higher risk for both symmetrical and asymmetrical head molding. This study involved 3D stereophotogrammetry to assess the cranial growth, molding, and incidence of deformational plagiocephaly (DP) in preterm children compared to term born children. Thirty-four preterm infants and 34 term born controls were enrolled in this study from Oulu University Hospital, Finland. Three-dimensional head images were obtained at the age of 2–4 months (T1), 5–7 months (T2), 11–13 months (T3), and 2.5–3 years (T4) from the term equivalent age (TEA). There was no statistically significant difference in oblique cranial length ratio (OCLR), cephalic index (CI), or weighted asymmetry score (wAS) between the two groups. Occipital flattening, defined by flatness score (FS) was statistically significantly greater in the preterm group than in the term group at T1–T4 (p < 0.05). In both groups, OCLR improved gradually over time. There were no instances, in either group, of severe DP and no moderate DP after T2. Results indicate that DP affects preterm and full-term children almost equally during the first three years of life, and cranial asymmetry resolves at a similar rate in both preterm and term groups after three months of corrected age. Preterm infants present with more occipital flattening than full-term children