Julia Emerson

Cytogenetics of 158 patients with regional or disseminated melanoma. Subset analysis of near-diploid and simple karyotypes.

We report on the cytogenetic analyses of 158 cases of metastatic malignant melanoma, comprised of 63 cases with regional disease (RD) and 95 cases with distant (metastatic) disease (DD). Clonal structural abnormalities were identified in 126 (80%) cases and were significantly increased ( < 0.01 after adjusting for multiple comparisons) on chromosomes (in order of frequency of involvement) 1, 6, 7, 11, 9, and 3. Clustering of breakpoints occurred at 1p36, 1p22-q21, 6p11-q21, 9p, 11q23-qter, 13p (especially for cases with DD), and 19q13. The most common clonal numerical abnormalities, in a subset of 49 near-diploid cases were -10, -22, -9, +7, -19, and -Y. Analysis of chromosome segment gains and losses (CSRP) showed frequent loss of chromosomes 6 and 10, followed by equal rates of involvement of chromosomes 1, 7, and 9. Whole or segmental losses of chromosome 9 (especially 9p) correlate well with recent molecular genetic studies identifying putative suppressor genes, and are also likely important genetic abnormalities. However, based on the frequency of abnormalities in this large series of metastatic melanomas, it is likely that structural abnormalities of 1 and 6, and 10 are important in the pathogenesis of sporadic advanced melanoma.

Amplification of 19q13.1-q13.2 sequences in ovarian cancer: G-band, FISH, and molecular studies

In this study of ovarian carcinoma, we extended previous findings by performing FISH using chromosome 19 paint and microFISH probes and patient samples with and without abnormalities of chromosome 19 identified by G-banding. Karyotype interpretations of der(19) were confirmed, while additional 19 translocations were also detected by FISH with 19WCP in some cases. Similar FISH studies of ovarian carcinoma cell lines found chromosome 19 abnormalities even after extensive in vitro culture. MicroFISH probes were generated by chromosome microdissection from two cases with hsr(19) and mapped to 19q13.2 and 19q13.1-.2, respectively. FISH with these microFISH probes alone or in combination with a 19WCP probe to four patient samples and seven cell lines showed that 65% of chromosome 19 structural abnormalities contained 19q13.1-q13.2 sequences, sometimes as large hsrs. Ovarian cancer cell lines showed amplification and overexpression of the AKT2 putative oncogene, but not the ERCC-2 DNA repair gene in this chromosomal region. In addition to AKT2, amplification and overexpression of other yet-unidentified genes in the 19q13.1-q13.2 region may contribute to ovarian carcinoma pathogenesis or progression.

Chromosome abnormalities in ovarian adenocarcinoma: I. Nonrandom chromosome abnormalities from 244 cases.

Cytogenetics provides important insights into the molecular pathogenesis of human cancers. Although extensive data exist on recurring cytogenetic abnormalities in hematologic cancers, data on individual solid tumor types remain limited. Previous studies of ovarian carcinoma indicated the presence of multiple, complex clonal chromosome abnormalities. Cytogenetics remains one of a few techniques capable of detecting these multiple, simultaneously occurring genetic abnormalities. We describe cytogenetic abnormalities from a series of 244 primary ovarian cancer specimens referred to a single institution. A total of 201/244 cases had fully characterized clonal chromosome abnormalities, of which 134 showed clonal chromosome breakpoints. We used a novel statistical technique to detect nonrandom chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints was detected at regions 1p1*, 1q1*, 1p2*, 1q2*, 1p3*, 1q3, 3p1*, 1q4*, 6q1*, 6p2, 6q2, 7p1*, 7q1, 7p2*, 11p1*, 11q1, 11q2*, 12p1, 12q2*, 13p1, and 19q1. Simultaneous occurrence of multiple abnormalities was common. However, 120/134 cases had breakpoints at one or more of 13 commonly involved regions (*), suggesting a hierarchy of genetic abnormalities. Among clinical and tumor variables that predict patient survival, tumor grade was significantly associated with the presence of chromosome breakpoints. In additional studies, we show that nonrandom chromosome abnormalities are associated with impaired survival in ovarian cancer and that specific, nonrandomly involved chromosome regions retain significant effects on survival when analyses are controlled for important clinical variables. Additional specific chromosome abnormalities in this series are described, including chromosome gains and losses in near‐diploid cases and homogeneously staining regions. These results suggest that recurring, nonrandom chromosome abnormalities are important in the pathogenesis and/or progression of ovarian cancers, and target areas of the genome for molecular genetic studies. Genes Chromosomes Cancer 25:290–300, 1999.

Educating preschoolers about sun safety.

OBJECTIVES This feasibility study examined whether a sun safety curriculum designed for and administered to preschoolers affects their cognition (knowledge, comprehension, application) regarding sun safety. METHODS Twelve classes of 4- to 5-year-olds were recruited from local preschools and randomly assigned to an intervention group or a control group. The intervention group received an investigator-developed sun safety curriculum; the control group did not. Children in both groups were tested at the beginning of the study about their cognition related to sun safety. They then received posttests 2 and 7 weeks following the pretest. RESULTS The curriculum had a significant effect on the knowledge (P = .01) and comprehension (P = .006) components of cognition. The application component of cognition was not significantly changed by the curriculum. CONCLUSIONS A structured curriculum was found to be an efficacious means of enhancing knowledge and comprehension of sun safety in preschool children. At the preoperational developmental stage, however, children may not be able to apply such knowledge and comprehension.

Clonal chromosome abnormalities in 54 cases of ovarian carcinoma

As a prelude to assessing the relationship of chromosome alterations to clinical outcome in ovarian carcinoma, we report on the cytogenetic analysis on short-term cultures from 54 patients. All patients had histopathologically confirmed malignancy, with the majority of cases demonstrating serous ovarian adenocarcinomas. Structural alterations were evident in 52 cases, whereas numeric changes were identified in 13 cases. The most notable numeric abnormalities were loss of the X-chromosome (9/13 total cases) and +7 (3/9 diploid cases). Structural alterations most frequently involved chromosomes 1, 3, 6, 7, 11, and 12. Chromosomal breakpoints were shown to cluster in several chromosomal banding regions, including 1p36, 1p11-q21, 3p23-p10, 7p (especially 7p22), 11p, 11q, 12p13-q12, and 12q24. The frequency of structural alterations involving the following chromosome arms was found to be significantly increased: 1p (p < 0.01), 7p (p < 0.01), 11p (p < 0.01), 11q (p < 0.05), and 12p (p < 0.05). An analysis of the net gain or loss of chromosome segments was also performed, with the most consistent tendency observed being over-representation of 1q and chromosome 7, deletion of 1p, and loss of the X chromosome.

Public education projects in skin cancer. The evolution of skin cancer prevention education for children at a comprehensive cancer center

Background. Skin cancer affects more Americans than any other type of cancer. Children are prime targets for prevention education, because sun overexposure in early childhood may affect the development of skin cancer later in life. Preventive behaviors adopted early in life may be less resistant to change than those acquired in adulthood. Thus, there is a need to educate children at an early age about sun overexposure.

Chromosome abnormalities in malignant melanoma:: clinical significance of nonrandom chromosome abnormalities in 206 cases

We report the cytogenetic abnormalities from a series of 206 primary malignant melanoma specimens referred to a single institution. A total of 169 out of 206 unique cases had chromosome breakpoints. A previously described statistical method was used to detect nonrandom distribution of chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints (indicating that the observed number of breaks significantly exceeded the expected number of breaks) was detected in 28 regions, suggesting a hierarchy of genetic abnormalities in melanoma. Clinical variables and tumor characteristics were analyzed for associations with the presence of any nonrandom chromosome breakpoints; with individual, nonrandomly involved chromosome regions; and with paired, nonrandomly involved chromosome regions. No nonrandomly involved chromosome regions or pairs of regions appeared to significantly affect survival. These results identify recurring, nonrandom chromosome abnormalities in malignant melanoma. These results suggest that recurring, nonrandom chromosome alterations play a key role in the etiology and/or progression of malignant melanoma and identify targets within the genome for molecular genetic studies.

Band 1p36 Abnormalities and t(1;17) in Ovarian Carcinoma

In a series of 128 karyotyped ovarian carcinomas, 42% of cases with chromosome 1 clonal structural abnormalities had breaks at band 1p36 (usually involving translocations of unknown material). Fluorescent in situ hybridization (FISH) studies using combinations of 1 centromere and 1p36.3-specific probes (16 cases) or 1 centromeric and 17 whole-chromosome paint probes (11 cases with 1p+) revealed a trend toward deletion of 1pter relative to 1 centromere (63%); intratumor heterogeneity; and the origin of 1p+ in 3/11 cases (27%) from chromosome 17 [t(1;17)(p36;?)]. The frequency of this specific breakpoint and its involvement in recurrent translocations suggest that these regions are loci for genes important in the pathogenesis of a subset of sporadic ovarian carcinomas.

Chromosome abnormalities in ovarian adenocarcinoma: II. Prognostic impact of nonrandom chromosome abnormalities in 244 cases

In a large series of ovarian carcinomas from 244 patients, 134 cases had chromosome rearrangements. We showed before that the pattern of chromosome breakpoints involved 21 separate chromosome regions nonrandomly and, in 90% of cases with breaks, the breakpoints occurred within 13 commonly involved regions. Log‐rank and proportional hazards regression analyses showed that the aggregate presence of a chromosome breakpoint in any of 21 nonrandomly involved regions and breaks in 9 distinct regions (1p1, 1q2, 1p3, 3p1, 6p2, 11p1, 11q1, 12q2, and 13p1) were associated with reduced patient survival. Breakpoints in other areas of the genome, including other nonrandomly involved regions, were not associated with decreased survival. Because many cases had breakpoints in more than one nonrandomly involved region, proportional hazards regression was also used to analyze for effects of each nonrandomly involved region, controlling for effects of other regions. With this approach, only breakpoints within 1p1 and 3p1 retained independent, deleterious effects on survival. Similarly, when nonrandomly involved regions were entered into a proportional hazards model containing clinical variables associated with altered patient survival (tumor grade, tumor stage, and residual disease >1 cm after resection), only 1p1 (P = 0.007) and 3p1 (P = 0.04) were associated with independent, negative effects on survival. These studies demonstrate that chromosome breakpoints within specific, nonrandomly involved chromosome regions are associated with impaired survival in ovarian cancers. Regions 1p1 and 3p1 are identified as areas of particular significance and are appropriate targets for analytical techniques such as SAGE and microarray analysis. Genes Chromosomes Cancer 25:46–52, 1999.

Dietary habits and the risk of stomach cancer: a comparison study of patients with and without intestinal metaplasia.

Patients with chronic atrophic gastritis intestinal metaplasia (IM) are suspected of being at increased risk for the intestinal type of gastric cancer. Diet is one of several etiologic components that may contribute to the development of the IM lesion. One hundred patients (50 with IM and 50 without IM) were evaluated to determine their dietary intake of nitrosating agents and vitamin C and their smoking habits. Patients with IM reported a higher consumption of two foods rich in nitrosating agents, bacon (.28 vs. .10, p = .02) and sausages (.16 vs. .02, p = .01), compared to patients without IM. Smoking and vitamin C intake were similar in both the IM-positive and the IM-negative groups.