The Innate Immune System Surveillance Biomarker p87 in African Americans and Caucasians with Small High-Grade Dysplastic Adenoma [SHiGDA] and Right-Sided Colon Mutations May Explain the Presence of Multiple Cancers Revealing an Important Minority of Patients with Mutations and Colorectal Neoplasia.

Unlabelled: Colorectal cancer (CRC) outcomes in terms of incidence and mortality are significantly worse in African Americans than other Americans. While differences in primary preventions for neoplasia (diet, obesity remediation, aspirin prophylaxis) are being elucidated, genetic mutations affecting premalignant lesions and immune response mechanisms may possibly also explain the increased incidence and mortality, particularly from right-sided disease.

Objective: Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions.

Uniparental disomy of multiple chromosomes in two cases with a complex phenotype.

Uniparental disomy (UPD) is the inheritance of both chromosomal homologs from one parent. Depending on the chromosome involved and the parental origin, UPD may result in phenotypic abnormalities due to aberrant methylation patterns or unmasking recessive conditions in isodisomic regions. UPD primarily originates from somatic rescue of a single meiotically-derived aneuploidy, most commonly a trisomy.

Aminoglycoside induced ototoxicity risk in the cystic fibrosis population: The utility of large-scale screening.

Background: MT-RNR1 variants are a well-known cause of aminoglycoside-induced hearing loss (AIHL). Individuals with cystic fibrosis (CF) routinely receive aminoglycosides and are at high risk of AIHL. However, genetic testing before treatment is not routinely performed due to perceived rarity of risk, and cost ineffectiveness with traditional technologies.

Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota.

The study of sex-specific genetic associations with opioid response may improve the understanding of inter-individual variability in pain treatments. We investigated sex-specific associations between genetic variation and opioid response. We identified participants in the RIGHT Study prescribed codeine, tramadol, hydrocodone, and oxycodone between 01/01/2005 and 12/31/2017.

Targeted Genotyping in Clinical Pharmacogenomics: What Is Missing?

Clinical pharmacogenomic testing typically uses targeted genotyping, which only detects variants included in the test design and may vary among laboratories. To evaluate the potential patient impact of genotyping compared with sequencing, which can detect common and rare variants, an in silico targeted genotyping panel was developed based on the variants most commonly included in clinical tests and applied to a cohort of 10,030 participants who underwent sequencing for CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, DPYD, SLCO1B1, TPMT, UGT1A1, and VKORC1. The results of in silico targeted genotyping were compared with the clinically reported sequencing results.

Germline mutations in apoptosis pathway genes in ovarian cancer; the functional role of a TP53I3 (PIG3) variant in ROS production and DNA repair.

Approximately 25% of all cases of ovarian cancer (OVCA) cases are associated with inherited risk. However, accurate risk assessment is limited by the presence of variants of unknown significance (VUS). Previously, we performed whole-exome sequencing on 48 OVCA patients with familial predisposition, yet negative for pathogenic BRCA1/2 mutations.

Most noninvasive prenatal screens failing due to inadequate fetal cell free DNA are negative for trisomy when repeated.

Objective: We aimed to test for an association between the amount of circulating fetal cell-free DNA and trisomy, and whether NIPS failure due to low fetal fraction indicates trisomy risk.

Method: Maternal BMI, maternal age, fetal sex, gestational age, fetal cfDNA fraction, and NIPS results was collected on 2374 pregnancies. Additional clinical information was available for 1180 research consented patients.

Characterizing false-positive fluorescence in situ hybridization results by mate-pair sequencing in a patient with chronic myeloid leukemia and progression to myeloid blast crisis.

Traditional cytogenetic testing methodologies, including conventional chromosome analysis and fluorescence in situ hybridization (FISH), are invaluable for the detection or recurrent genetic abnormalities in various hematologic malignancies. However, technological advances, including a novel next-generation sequencing technique termed mate-pair sequencing (MPseq), continue to revolutionize the field of cytogenetics by enabling the characterization of structural variants at a significantly higher resolution compared to traditional methodologies. To illustrate the power of MPseq, we present a 27-year-old male diagnosed with chronic myeloid leukemia in myeloid blast crisis with multiple chromosomal abnormalities observed in all 20 metaphases from a peripheral blood specimen, including t(9;22)(q34;q11.

FANCM, RAD1, CHEK1 and TP53I3 act as BRCA-like tumor suppressors and are mutated in hereditary ovarian cancer.

Although 25% of ovarian cancer cases are due to inherited factors, most of the genetic risk remains unexplained. We previously identified candidate genes through germline whole exome sequencing of BRCA1/BRCA2 negative ovarian cancer patients with familial risk. Here, we performed functional assessment to determine whether they act as BRCA-like tumor suppressors.