Springer Nature

Congenital anomalies (CA), developmental delay (DD), and intellectual disability (ID) are among the most common indicators in children that lead to genetic testing. Identification of an underlying diagnosis for CA or DD/ID can be consequential to care management and long-term prognosis for the child. But there has been no evidence-based guideline for clinicians to refer to that supports the use of exome or genome sequencing as a first-line or second-line test for the evaluation of pediatric patients with CA or DD/ID.

On this month’s GenePod, Fuki Hisama, MD, FACMG, FAAN and Murugu Manickam, MD, FACMG, who co-chaired the American College of Medical Genetics and Genomics (ACMG) evidence-based work group, discuss how a team of experts was brought together to provide the ACMG’s first ever evidence-based clinical guideline. This guideline lays out clear recommendations for use of exome or genome sequencing in clinical care to optimize outcomes for pediatric patients with CA or DD/ID. “In a way, this model of an evidence-based guideline is creating the standard and a template for future studies” says Dr. Manickam.

Dr. Sabina Berezowka, from the university of Lausanne Switzerland, discusses with our host her team’s recent study describing a novel “Prognostic Score” for assessing tumor regression following Neaodjuvant therapy in non-small cell lung cancer (NSCLC).

The proposed combined prognostic score (PRSC) performed better than pTNM staging and previously published Major Pathologic Response (MPR) approach.

Study by Berezowka et al, A prognostic score for non-small cell lung cancer resected after neoadjuvant therapy in comparison with the tumor-node-metastases classification and major pathological response. Modern Pathology, 34, 1333–1344, 2021. https://www.nature.com/articles/s41379-021-00777-y.

Dr. Jason Hornick discusses his team recent study finding that a monoclonal antibody directed against the N-terminus of DDIT3 is a highly sensitive and specific for high-grade MLPS. DDIT3 immunostains could replace molecular genetic testing in many cases, although limited labeling may be seen in a range of other tumor types.

Always a visionary, Dr. Reuter was one of the earliest Anatomic Pathologists to embrace and advance the genomic and more recently the digital transformation of our field.

In this episode of Meet The Expert series, Dr. Reuter shares his perspective and vision on the current and future impact of digital pathology.

In this episode Dr. Rohit Mehra of University of Michigan discusses the utility of TRIM63 as a diagnostic marker to distinguish MiTF-RCC from other renal tumor subtypes with overlapping morphology. In combination with TFE3/TFEB FISH, TRIM63 RNA-ISH assays can improve the accuracy and efficiency of MiTF-RCC diagnosis.

Associated article: TRIM63 is a sensitive and specific biomarker for MiT family aberration-associated renal cell carcinoma. https://www.nature.com/articles/s41379-021-00803-z

Dr. Clare Verrill and Andrea Chatrian of Oxford University in England discuss their team’s study on AI for advance ordering of IHC in difficult prostate biopsy. Their elegant work shows that an AI tool making automated IHC request prior to the pathologist read of H&E could create leaner workflow and result in pathologist time savings and shorten overall Turnaround time from accession to final diagnosis.

Associated article: Artificial intelligence for advance requesting of immunohistochemistry in diagnostically uncertain prostate biopsies. https://www.nature.com/articles/s41379-021-00826-6

Dr. Britta Weigelt of MSKCC discusses her team’s study on synchronous endometrial (EC) and ovarian carcinomas (OC) in Lynch syndrome and constitutional Mismatch Repair Deficiency Syndrome (CMMRD). Contrary to sporadic synchronous ECs/OCs, which are almost invariably clonally related, ECs/OCs simultaneously involving the uterus and ovary in LS patients may represent two independent primary tumors. Like their sporadic counterparts, a subset of MMR deficiency syndrome-related synchronous ECs/OCs may also originate from a single with the endometrium being the likeliest site of origin. Associated article: Clonal relationship and directionality of progression of synchronous endometrial and ovarian carcinomas in patients with DNA mismatch repair-deficiency associated syndromes. https://www.nature.com/articles/s41379-020-00721-6

Red sea bream are an important fish in Japan, for both culinary and cultural reasons. But there’s a problem: transparent fish are appearing in fish farms! Join Dr Eitaro Sawayama (Nihon University) and find out how he uncovered the causative gene for this deformity, and what his work means for red sea bream aquaculture.

Associated article: Identification of the causative gene of a transparent phenotype of juvenile red sea bream Pagrus major https://www.nature.com/articles/s41437-021-00448-3

After more than 150 years, wolves once again roam the Germany countryside! Of course, a lot has changed in that time. Join Anne Jarausch (Senckenberg Research Institute and Natural History Museum Frankfurt) as she discusses her recent work looking at the genetics of this ongoing, rapid and natural wolf recolonisation.

Associated article: How the west was won: genetic reconstruction of rapid wolf recolonization into Germany’s anthropogenic landscapes https://www.nature.com/articles/s41437-021-00429-6

Join us as we talk to the newest member of the Heredity editorial board: Prof. Sam Banks (Charles Darwin University). Discover his eclectic research tastes, hear about his recent Heredity paper on Australia’s threatened brush-tailed rabbit-rat, and be inspired by his passion for population genetics and ecology.

Associated article: Population genomics and conservation management of a declining tropical rodent https://www.nature.com/articles/s41437-021-00418-9