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Simple Summary Since it was first described over two decades ago, the Alternative Lengthening of Telomeres (ALT) pathway has been well accepted to hold clinical significance in cancer development, cancer diagnosis, and cancer treatment. In this review, first, we discuss how the activation of this pathway is determined. Then, we provide up-to-date statistics on the cancers ALT activity is detected in. We discuss the relationships between ALT positivity and prognosis as well as the pathogenetics of ALT positive cancers. Finally, we evaluate pre-clinical and clinical investigations of potential therapies targeting ALT. Abstract Many exciting advances in cancer-related telomere biology have been made in the past decade. Of these recent advances, great progress has also been made with respect to the Alternative Lengthening of Telomeres (ALT) pathway. Along with a better understanding of the molecular mechanism of this unique telomere maintenance pathway, many studies have also evaluated ALT activity in various cancer subtypes. We first briefly review and assess a variety of commonly used ALT biomarkers. Then, we provide both an update on ALT-positive (ALT+) tumor prevalence as well as a systematic clinical assessment of the presently studied ALT+ malignancies. Additionally, we discuss the pathogenetic alterations in ALT+ cancers, for example, the mutation status of ATRX and DAXX, and their correlations with the activation of the ALT pathway. Finally, we highlight important ALT+ clinical associations within each cancer subtype and subdivisions within, as well as their prognoses. We hope this alternative perspective will allow scientists, clinicians, and drug developers to have greater insight into the ALT cancers so that together, we may develop more efficacious treatments and improved management strategies to meet the urgent needs of cancer patients.

Breast Cancer 1 (BRCA1) gene is a well-characterized tumor suppressor gene, mutations of which are primarily found in women with breast and ovarian cancers. BRCA1-associated RING domain 1 (BARD1) gene has also been identified as an important tumor suppressor gene in breast, ovarian, and uterine cancers. Underscoring the functional significance of the BRCA1 and BARD1 interactions, prevalent mutations in the BRCA1 gene are found in its RING domain, through which it binds the RING domain of BARD1. BARD1-BRCA1 heterodimer plays a crucial role in a variety of DNA damage response (DDR) pathways, including DNA damage checkpoint and homologous recombination (HR). However, many mutations in both BARD1 and BRCA1 also exist in other domains that significantly affect their biological functions. Intriguingly, recent genome-wide studies have identified various single nucleotide polymorphisms (SNPs), genetic alterations, and epigenetic modifications in or near the BARD1 gene that manifested profound effects on tumorigenesis in a variety of non-breast and non-gynecological cancers. In this review, we will briefly discuss the molecular functions of BARD1, including its BRCA1-dependent as well as BRCA1-independent functions. We will then focus on evaluating the common BARD1 related SNPs as well as genetic and epigenetic changes that occur in the non-BRCA1-dominant cancers, including neuroblastoma, lung, and gastrointestinal cancers. Furthermore, the pro- and anti-tumorigenic functions of different SNPs and BARD1 variants will also be discussed.

Background: To present a retrospective study on the outcomes of a modified version of suture suspension arthroplasty with trapeziectomy on patients with thumb basal joint arthritis and to evaluate the relationship between the degree of subsidence and functional outcome. Methods: We performed a chart review on 67 patients (75 thumbs) who were surgically treated for thumb carpometacarpal osteoarthritis with trapeziectomy and suture suspension arthroplasty from May 2010 to May 2016. Outcome measures included Disabilities of the Arm, Shoulder and Hand (DASH), grip strength, lateral/precision pinch strength, range of motion, and return to work/resumption of usual activities. Radiographic images were used to measure first metacarpal subsidence into the trapezial space. Results: Clinical outcomes were satisfactory, showing an initial postoperative DASH score of 45.94, which decreased to 27.93 at 6 months postoperatively and to 19.69 at 1 year postoperatively. Radiographic images revealed a mean first metacarpal subsidence of 39% compared with the preoperative images. Grip and pinch strengths showed steady improvement from initial postoperative to final follow-up visits, resulting in 90% recovery of gross grasp, 77% recovery of lateral pinch, and 79% recovery of precision pinch compared with the contralateral side. Conclusions: Our study has found that suture suspension arthroplasty with trapeziectomy is an effective treatment for thumb basal joint arthritis. Suture suspension arthroplasty allows for short immobilization time, avoids tendon sacrifice, avoids anchor use, and leaves a cosmetically appealing scar. Furthermore, a relationship of any significance between postoperative first metacarpal subsidence and functional outcomes does not appear.