PROTAC resistance in cancer cells is mediated by MDR1 drug efflux activity

Selectively inhibiting protein function through proteolysis-targeting chimeras (PROTACs) has emerged as a novel cancer therapeutic strategy. PROTACs are small molecules with two active domains that bind to an E3 ubiquitin ligase and a protein of interest, which results in the ubiquitination and subsequent degradation of the protein of interest...


Known cancer driver mutations found in endometrial polyps at low allelic frequencies

Endometrial polyps (EMPs) are localized overgrowths of endometrial tissue that are composed of endometrial glands, stroma, and blood vessels. The reported prevalence of EMPs increases with age and ranges from 8-35%, depending on the population studied. EMPs are generally considered to be benign, with risk of malignancy around 3%. However, EMPs have been associated with several endometrial cancers...


Loss of chromosome Y linked to AML and clonal hematopoiesis

Mosaic loss of chromosome Y (mLOY) is the most common form of clonal mosaicism and is recurrent in the blood cells of adult males. This chromosome alteration typically increases with age and has been linked with aging-related diseases including clonal hematopoiesis (CH), in which a single hematopoietic stem and progenitor cell (HSPC) gives rise to a genetically distinct subpopulation of peripheral blood or bone marrow cells, and acute myeloid leukemia (AML). ..


PDGFRA mutation increases cell proliferation in vitro via an oncogenic splice variant

The era of personalized medicine and genome-based cancer therapies has been accelerated by next-generation sequencing technologies, which allow for the identification of gene variants with clinical implications for diagnosis, prognosis, and patient care. However, many newly identified variants have yet to be linked to disease, and these are referred to as variants of uncertain significance (VUS)...


Oncogenic lncRNA PCAT2 linked to chromosome instability in cancer

hromosome breaks and translocations are often critical factors in tumorigenesis and cancer progression. One primary contributor to these types of chromosomal instability is the mis-regulation of histone proteins. Histones are responsible for packaging the human genome into chromatin and can be divided into five main families: H1/H5, H2A, H2B, H3, and H4...


Empire Genomics Welcomes Andre Lubarsky as US Sales Director

July 20th, Buffalo, NY – Empire Genomics, a company that develops high-quality molecular probes for fluorescent and chromogenic in situ hybridization testing, has selected Andre Lubarsky to initiate the new North American business development strategy as Director of Sales. Andre is a seasoned sales director, most recently with System Biosciences, Inc., who will now be leveraging his experience to develop and execute key growth sales strategies in the United States and North America...


SUCLG2 proposed as biomarker in pheochromocytoma and paraganglioma

Pheochromocytoma, a neuroendocrine tumor of the adrenal medulla, and paraganglioma, a tumor derived from neural crest progenitor cells outside the adrenal gland, have a strong genetic basis, with up to 40% of cases displaying germline mutations and another 25-30% carrying a somatic mutation. ..


Point mutation causes dramatic shift in HIV-1 integration sites

Retroviruses, such as the human immunodeficiency virus (HIV-1), insert a copy of their genome into the host cell genome during a process called integration. This allows retroviruses to persist indefinitely in the infected cell as a provirus. During integration, the virally encoded integrase (IN) protein binds to various host factors that likely act as a tether between the viral IN protein and the host chromatin at the integration site...


DTX3 amplification found in a small proportion of breast cancer patients; linked with increased proliferation

The degree of cell proliferation is one of the most powerful prognostic features in breast cancer. Deltex E3 ubiquitin ligase 3 (DTX3), a member of the Deltex family, is located on 12q13.3 and is involved in neurogenesis and Notch signaling. DTX3 has been suggested as a potential driver gene of cell proliferation in luminal subtypes of breast cancer and has been associated with poor prognosis. However, studies of DTX3 in different cancers have found different results; in esophageal cancer, DTX3 was associated with reduced proliferation of tumor cells, and in colorectal cancer, DTX3 was proposed as an endogenous control gene for gene expression analyses...


Plott syndrome caused by an interchromosomal insertion

Plott syndrome, or familial congenital bilateral laryngeal abductor paralysis, was first described by Plott and colleagues in 1964 and has been reported twice since that time. Clinical expression has been limited to male children, and inheritance patterns have suggested Plott syndrome to be an X-linked recessive disorder. However, no conclusive genetic or chromosomal aberration has been reported to date, and no genetic tests have been conducted on any of the affected families. In this case, the authors report a new family with Plott syndrome and present data to suggest that Plott syndrome is caused by a 404kb fragment inserted into the intergenic chromosomal region Xq27.1...


Clonal heterogeneity and specific chromosome gains proposed as new prognostic biomarkers for HHD-B-ALL

B-cell acute lymphoblastic leukemia (B-ALL), the most common childhood cancer, features a substantial subgroup of patients with chromosomal gains (hyperdiploidy). Patients with a modal chromosome number >50 (high hyperdiploidy; HHD) account for nearly 30% of B-ALL cases and typically have a more favorable prognosis. Although HHD represents an important prognostic factor in childhood B-ALL, the specific chromosome gains that most contribute to a favorable clinical outcome have yet to be established...


Unique Extra-Oral Case of Microsecretory Adenocarcinoma

The patient originally presented for treatment of benign paroxysmal positional vertigo. A painless mass in her right external ear canal was identified, and further examination revealed an obstructing, friable lesion causing cerumen impaction. ..


First Report of an APP Locus Triplication Causing Early-Onset CAA and AD

The accumulation of amyloid-β precursor protein (Aβ) plaques is characteristic of both cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD). Duplications of the amyloid-β precursor protein (APP) gene, which is located on 21q21.3, have been linked to early onset CAA and/or early onset AD...


Associations Between CCND1 Amplification in Breast Cancer & Proliferation Status

Breast cancer is a highly heterogeneous disease that differs greatly between patients. As such, there is a need for new biomarker discovery that would allow for individualized diagnoses, treatments, and prognoses for breast cancer patients. In this study, the authors assessed the ability of CCND1 amplification to serve as a prognostic biomarker in breast cancer...


ZNF703 Copy Number Linked to Poor Prognosis in Breast Cancer

Among patients with breast cancer, luminal subtypes are the most common. Differences in prognosis have been demonstrated between the luminal subtypes, ranging from patients with an excellent prognosis to those who require much more aggressive treatment. ..


Clinicopathological Characterization of Renal Cell Carcinoma in Young Adults: a contemporary update and review of literature

A continuous challenge for cancer researchers is conducting analyses in age groups where cases are limited. Renal cell carcinoma (RCC) is a kidney cancer that occurs in individuals of all ages, but is far more prevalent in older patients. Because of this, research on young adult and childhood RCC (in particular, morphological and genetic characterization studies) has been scant. ..

Dr. Rohit Mehra


Hydropic leiomyoma: a distinct variant of leiomyoma closely related to HMGA2 overexpression

Uterine leiomyoma (ULM) is the most prevalent benign tumor of the female reproductive system, occurring in up to 70% of pre-menopausal women. Several different subtypes have been identified, including hydropic leiomyoma (HLM). Certain aspects of HLM’s morphology make it difficult to identify – particularly, cases with extensive hydropic change can hide features typical of leiomyoma, making diagnosis tricky...

Dr. Brannan B. Griffin


Pediatric acute myeloid leukemia with t(7;21)(p22;q22)

Pediatric acute myeloid leukemia (AML) accounts for about 25% of childhood cancer cases. While survival rates have risen dramatically in the past few decades, 30% of patients still experience relapse. Fortunately, recent studies have uncovered a variety of genetic abnormalities specific to the disease that both (A) provide important hints about its pathogenic/clinical course and (B) may serve as therapeutic targets for future treatment...

Dr. Prabakaran Paulraj


Analysis of NTRK Alterations in Pan-Cancer Adult and Pediatric Malignancies: Implications for NTRK-Targeted Therapeutics

We now understand that cancer is a disease rooted in genomic breakdown. But when analyzing a patient’s genome, not all mutations contribute equally to disease. Further complicating things is the fact that, even after a gene’s role in cancer development is clearly established, only certain alterations can be targeted by current therapies. Therapeutically targetable mutations, therefore, are needles in the haystack for cancer researchers – which explains the recent excitement around the NTRK gene family...

Dr. Ryosuke Okamura


Somatic and germline genomics in paediatric acute lymphoblastic leukaemia

The interplay between hereditary and somatic mutations in cancer development has been a difficult relationship for oncologists to unravel. While we now know that some cancers are indeed heritable, we don’t always know to what degree. Pediatric acute lymphoblastic leukemia (ALL) is one such disease, with a well-documented but still ambiguous hereditary component. A new study out of St. Jude’s Research Hospital – Somatic and germline genomics in paediatric acute lymphoblastic leukaemia (ALL) - expanded on the complex genetics of the disease. ..

Dr. Ching-Hon Pui


Infantile NTRK-Associated Mesenchymal Tumors

Infantile fibroblastic and myofibroblastic tumors are the second most prevalent type of soft tissue neoplasms in pediatric patients < 1 years old. Although the majority of these tumors are either benign or low-grade, there are certain subtypes with a higher tendency toward malignancy. Congenital infantile fibrosarcoma (CIFS) is one such high-risk group. CIFS patients, who are nearly always less 2 years old, present with morphologically ambiguous tumors that can resemble a range of other infantile neoplasms of varying clinical course, including myofibroma/myofibromatosis, lipofibromatosis and fibrous hamartoma of infancy, primitive myxoid mesenchymal tumor of infancy (PMMTI), and dermatofibrosarcoma protuberans (DFSP)...

Dr. Jessica Davis


Alterations in ALK / ROS1 / NTRK / MET Drive a Group of Infantile Hemispheric Gliomas

Gliomas are rare brain tumors that can affect individuals of all ages. While studies are plentiful on pediatric and adult gliomas, infant cases are historically understudied – an unfortunate fact, considering central nervous system tumors are most common (and deadly) in this age group. This research team sought to account for that lack of data by cytogenetically analyzing infant glioma samples collected between 1986 and 2017. The team was able to divide these tumors into three genetic subtypes that were tightly tied to clinical outcome. Additionally, they found that many of the tumors harbored just a single genetic aberration, evidence that infant gliomas are usually single driver tumors...

Dr. Cynthia Hawkins