Germline mutations in the BRCA1 and BRCA2 genes are strong genetic factors for predispositions to breast, ovarian, and other related cancers. This report describes a family with a history of breast and ovarian cancers that harbored a novel BRCA1 germline mutation. A single nucleotide deletion in intron 20, namely c.5332+4delA, was detected in a 43-year-old patient with breast cancer. This mutation led to the skipping of exon 20, which in turn resulted in the production of a truncated BRCA1 protein that was 1773 amino acids in length. The mother of the proband had died due to ovarian cancer and had harbored the same germline mutation. Ectopically expressed mutant BRCA1 protein interacted with the BARD1 protein, but showed a reduced transcriptional function, as demonstrated by the expression of cyclin B1. This novel germline mutation in the BRCA1 gene caused familial breast and ovarian cancers.
Adult ; Amino Acids ; BRCA1 Protein ; Breast Neoplasms* ; Breast* ; Cyclin B1 ; Exons* ; Genes, BRCA1 ; Genes, BRCA2 ; Germ-Line Mutation* ; Humans ; Introns ; Mothers ; Ovarian Neoplasms

PURPOSE: Unclassified variants (UVs) of BRCA1 and BRCA2 genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. Therefore, this study was conducted to identify potentially pathogenic UVs by comparing their prevalence between breast cancer patients and controls. MATERIALS AND METHODS: A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. Genetic variants of BRCA genes that were categorized as unclassified according to the Breast Cancer Information Core database were selected based on allelic frequency, after which candidate variants were genotyped in 421 healthy controls. We also examined family members of the study participants. Finally, the effects of amino acid substitutions on protein structure and function were predicted in silico. RESULTS: Genetic tests revealed 33 UVs in BRCA1 and 47 in BRCA2. Among 15 candidates genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 were not detected. Moreover, the c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal domain was predicted to have an effect on BRCA1 protein structure/function. CONCLUSION: This study showed that comparison of genotype frequency between cases and controls could help identify UVs of BRCA genes that are potentially pathogenic. Moreover, ourfindings suggest that c.5339T>C in BRCA1 might be a pathogenic variant for patients and their families.
Amino Acid Substitution ; BRCA1 Protein ; Breast Neoplasms* ; Breast* ; Computer Simulation ; Genes, BRCA1 ; Genes, BRCA2* ; Genetic Testing ; Genotype ; Humans ; Korea ; Prevalence

PURPOSE: Inguinal hernias are common in children and sometimes are associated with dangerous complications, such as incarceration. There are no established management guidelines for ovarian hernias. We have reviewed the clinical course of ovarian hernias in infants. METHODS: We reviewed the medical records of female infants diagnosed with ovarian hernias by ultrasonogram at Kwandong University College of Medicine, Cheil General Hospital, and the Women's Healthcare Center between March 2001 and August 2007. We analyzed the patients gestational age, birth weight, age at the time of detection of the inguinal mass, the patients chief complaints, operative time, post-operative complications, and ultrasonographic findings. RESULTS: Eight female infants had ovarian hernias, four of whom were born prematurely. Seven infants had left-sided ovarian hernias, and one infant had a right-sided ovarian hernia. Five infants underwent surgery and there were no postoperative complications or recurrences. Three girls did not have surgery, and the ovarian hernias regressed spontaneously, with no recurrences or complications. The regression time of inguinal masses ranged from 70-161 days after birth. CONCLUSION: Physical examination to detect movable masses within the labium major in premature female infants is important because the incidence of premature inguinal hernias is much higher than in term infants. No rational medical treatment plans for female ovarian hernias have been published to date. We cared for three girls with spontaneous regression of ovarian hernias. Pediatricians should be aware whether emergent surgery for ovarian hernias is indicated.
Birth Weight ; Child ; Delivery of Health Care ; Female ; Gestational Age ; Hernia ; Hernia, Inguinal ; Hospitals, General ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Medical Records ; Operative Time ; Ovary ; Parturition ; Physical Examination ; Postoperative Complications ; Recurrence

PURPOSE: It has been described that the incidence of breastfeeding jaundice is 13% and that of breast milk jaundice is 2%. The incidence in Korea was believed to be higher, but there were no studies to prove this assumption. The purpose of this study was to investigate the incidence of jaundice of healthy breastfed full-term infants in Korea. METHODS: 839 infants were enrolled who were admitted to the Postpartum Care Center of the Cheil General Hospital between January 1 and December 31, 2005, and were followed up for more than 7 days. Those infants were divided into 3 groups; Exclusive breastfeeding group; Partial breastfeeding group; Formula feeding group. If they became icteric, transcutaneous bilirubin (TcB) was measured by research nurses with JM-103 Jaundice meter (Konica Minolta sensing, Inc., Osaka, Japan). Using this method we investigated the incidence of breast milk jaundice of healthy breastfed full-term infants. RESULTS: There were no significant differences in sex, birth weight, Apgar score, or obstetric risk factors among 3 groups but there were higher rates of vaginal delivery in the exclusive breastfeeding group. The incidence of breast milk jaundice was 10.8% in the exclusive breastfeeding group and 4.4% in the partial breastfeeding group. The incidence of breast milk jaundice in the breastfed infants was 6.3%. The incidence was significantly higher in the exclusive breastfeeding group than in the partial breastfeeding group. CONCLUSION: The incidence of breast milk jaundice of healthy breastfed full-term infants was 6.3%. It was found that the incidence of breast milk jaundice was higher in this study than in other countries. But it was not a population-based study, so further study with the large sample sizes is needed.
Apgar Score ; Bilirubin ; Birth Weight ; Breast Feeding ; Breast* ; Hospitals, General ; Humans ; Incidence* ; Infant* ; Jaundice* ; Korea ; Milk, Human* ; Postnatal Care ; Risk Factors ; Sample Size

PURPOSE: It has been described that the incidence of breastfeeding jaundice is 13% and that of breast milk jaundice is 2%. The incidence in Korea was believed to be higher, but there were no studies to prove this assumption. The purpose of this study was to investigate the incidence of jaundice of healthy breastfed full-term infants in Korea. METHODS: 839 infants were enrolled who were admitted to the Postpartum Care Center of the Cheil General Hospital between January 1 and December 31, 2005, and were followed up for more than 7 days. Those infants were divided into 3 groups; Exclusive breastfeeding group; Partial breastfeeding group; Formula feeding group. If they became icteric, transcutaneous bilirubin (TcB) was measured by research nurses with JM-103 Jaundice meter (Konica Minolta sensing, Inc., Osaka, Japan). Using this method we investigated the incidence of breast milk jaundice of healthy breastfed full-term infants. RESULTS: There were no significant differences in sex, birth weight, Apgar score, or obstetric risk factors among 3 groups but there were higher rates of vaginal delivery in the exclusive breastfeeding group. The incidence of breast milk jaundice was 10.8% in the exclusive breastfeeding group and 4.4% in the partial breastfeeding group. The incidence of breast milk jaundice in the breastfed infants was 6.3%. The incidence was significantly higher in the exclusive breastfeeding group than in the partial breastfeeding group. CONCLUSION: The incidence of breast milk jaundice of healthy breastfed full-term infants was 6.3%. It was found that the incidence of breast milk jaundice was higher in this study than in other countries. But it was not a population-based study, so further study with the large sample sizes is needed.
Apgar Score ; Bilirubin ; Birth Weight ; Breast Feeding ; Breast* ; Hospitals, General ; Humans ; Incidence* ; Infant* ; Jaundice* ; Korea ; Milk, Human* ; Postnatal Care ; Risk Factors ; Sample Size

The vibrational spectral differences of normal and lung cancer cells were studied for the development of effective cancer cell screening by means of attenuated total reflection infrared spectroscopy. The phosphate monoester symmetric stretching nus(PO3(2-)) band intensity at ~970 cm-1 and the phosphodiester symmetric stretching nus(PO2-) band intensity at ~1,085 cm-1 in nucleic acids and phospholipids appeared to be significantly strengthened in lung cancer cells with respect to the other vibrational bands compared to normal cells. This finding suggests that more extensive phosphorylation occur in cancer cells. These results demonstrate that lung cancer cells may be prescreened using infrared spectroscopy tools.
*Carcinoma ; Cell Line, Tumor ; Epithelial Cells/*physiology ; Humans ; *Lung Neoplasms ; Respiratory Mucosa/*cytology ; *Spectrophotometry, Infrared

PURPOSE: Defects in the DNA damage repair process can cause genomic instability and play an important role in cervical carcinogenesis. The purpose of this study was to analyze the association of 29 candidate single nucleotide polymorphisms (SNPs) in genes in the DNA repair pathway, TP53, and TP53BP1 with the risk of cervical cancer. MATERIALS AND METHODS: Twenty-nine SNPs in four genes in the DNA repair pathway (ERCC2, ERCC5, NBS1, and XRCC1), TP53, and TP53BP1 were genotyped for 478 cervical cancer patients and 922 healthy control subjects, and their effects on cervical carcinogenesis were analyzed. RESULTS: The most significant association was found for rs17655 in ERCC5, with an age-adjusted p-value < 0.0001, for which a strong additive effect of the risk allele C was observed (odds ratio, 2.01 for CC to GG). On the other hand, another significant polymorphism rs454421 in ERCC2 showed a dominant effect (odds ratio, 1.68 for GA+AA to GG) with an age-adjusted p-value of 0.0009. The association of these polymorphisms remained significant regardless of the age of onset. The significant result for rs17655 was also consistent for subgroups of patients defined by histology and human papillomavirus (HPV) types. However, for rs454421, the association was observed only in patients with squamous cell carcinoma and non-HPV 18 type. CONCLUSION: The results of this study show a novel association of cervical cancer and the genes involved in the nucleotide excision pathway in the Korean population.
Age of Onset ; Alleles ; Carcinogenesis ; Carcinoma, Squamous Cell ; DNA Damage ; DNA Repair* ; Genomic Instability ; Hand ; Humans ; Polymorphism, Single Nucleotide ; Uterine Cervical Neoplasms*

Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells, of which the prognostic factors include chromosomal abnormality, β-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event. Many studies have shown an association of chromothripsis with the prognosis in several cancers; however, few studies have investigated it in MM. Here, we studied the association between chromothripsis-like patterns and treatment resistance or prognosis. First, we analyzed nine MM cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS-28-PE, and NCI-H929) and bone marrow samples of four patients who were diagnosed with MM by next-generation sequencing-based copy number variation analysis. The frequency of the chromothripsis-like pattern was observed in seven cell lines. We analyzed the treatment-induced chromothripsis-like patterns in KMS-12-BM and KMS-12-PE cells. As a result, breakpoints and chromothripsis-like patterns were increased after drug treatment in the relatively resistant KMS-12-BM. We further analyzed the patients’ results according to the therapeutic response, which was divided into sensitive and resistant, as suggested by the International Myeloma Working Group. The chromothripsis-like pattern was more frequently observed in the resistant group. In the sensitive group, the frequency of the chromothripsis-like pattern decreased after treatment, whereas the resistant group showed increased chromothripsis-like patterns after the treatment. These results suggest that the chromothripsis-like pattern is associated with treatment response in MM.
Bone Marrow ; Cell Line ; Chromosome Aberrations ; Drug Resistance ; Humans ; Multiple Myeloma* ; Plasma Cells ; Prognosis

Interleukin-10 (IL10) plays an important role in initiating and maintaining an appropriate immune response to non-Hodgkin lymphoma (NHL). Previous studies have revealed that the transcription of IL10 mRNA and its protein expression may be infl uenced by several single-nucleotide polymorphisms in the promoter and intron regions, including rs1800896, rs1800871, and rs1800872. However, the impact of polymorphisms of the IL10 gene on NHL prognosis has not been fully elucidated. Here, we investigated the association between IL10 polymorphisms and NHL prognosis. This study involved 112 NHL patients treated at the National Cancer Center, Korea. The median age was 57 years, and 70 patients (62.5%) were men. Clinical characteristics, including age, performance status, stage, and extra-nodal involvement, as well as cell lineage and International Prognostic Index (IPI), were evaluated. A total of four polymorphisms in IL10 with heterozygous alleles were analyzed for hazard ratios of overall survival (OS) and progression-free survival (PFS) using Cox proportional hazards regression analysis. Diffuse large B-cell lymphoma was the most common histologic type (n = 83), followed by T-cell lymphoma (n = 18), mantle cell lymphoma (n = 6), and others (n = 5). Cell lineage, IPI, and extra-nodal involvement were predictors of prognosis. In the additive genetic model results for each IL10 polymorphism, the rs1800871 and rs1800872 polymorphisms represented a marginal association with OS (p = 0.09 and p = 0.06) and PFS (p = 0.05 and p = 0.08) in B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). These findings suggest that IL10 polymorphisms might be prognostic indicators for patients with B-cell NHL treated with R-CHOP.
Alleles ; B-Lymphocytes* ; Cell Lineage ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Humans ; Interleukin-10* ; Introns ; Korea ; Lymphoma, B-Cell* ; Lymphoma, Mantle-Cell ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell ; Male ; Models, Genetic ; Polymorphism, Single Nucleotide ; Prednisone ; Prognosis* ; Rituximab ; RNA, Messenger ; Vincristine

BACKGROUND: The aim of this study was to investigate the status of BRCA1/2 genetic testing practices in Korea in 2014. METHODS: A structured questionnaire was provided to the specialist in charge of BRCA1/2 genetic testing via e-mail between 28 July and 10 August 2015. A total of 11 genetic testing professionals from 14 organizations responded to the survey that asked about the status of BRCA1/2 genetic testing in the year 2014. RESULTS: The average number of BRCA1/2 genetic tests executed was 192; 6 organizations had executed less than 100 tests, and 5 organizations had conducted more than 100 tests. The primary testing method used was Sanger sequencing (100%), and 2 institutes performed multiplex ligation-dependent probe amplification (MLPA). The analysis software differed across the various organizations, with Sequencher (81.81%), Seqscape (27.27%), and Codoncode Aligner (9.09%) reported as utilized. We found that the guidelines for the interpretation of the genetic tests were different at each institution. CONCLUSIONS: Although this study only examined the status of the 2014 BRCA1/2 genetic testing practices of 11 institutions, it illustrates the necessity for standardized genetic testing or interpretation guidelines in Korea.
Academies and Institutes ; Electronic Mail ; Genetic Testing* ; Korea* ; Methods ; Multiplex Polymerase Chain Reaction ; Specialization ; Surveys and Questionnaires