Identification of a de novo ANK1 Variant in a Patient with Hereditary Spherocytosis on Multi-gene Panel Testing

AbstractPurpose: Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC. Methods: 302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83–66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58–23.95; P < 0.0001); and ATM: OR = 8.01 (95%CI 2.52–29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2. Conclusion: The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC.

Download Full-text

Clinical utility of a sponsored, no-cost skeletal dysplasia gene panel testing program: Results from 850 tests

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2020.12.238 ◽

2021 ◽

Vol 132 (2) ◽

pp. S98

Author(s):

Guillermo Seratti ◽

Vikram Pansare ◽

Tiffany Yar Pang ◽

Emanuela Izzo ◽

William Mackenzie ◽

...

Keyword(s):

Skeletal Dysplasia ◽

Clinical Utility ◽

Gene Panel ◽

Testing Program ◽

Panel Testing ◽

Gene Panel Testing

Download Full-text

Clinical utility of a sponsored, no-cost skeletal dysplasia gene panel testing program: results from 850 tests

Molecular Genetics and Metabolism ◽

10.1016/s1096-7192(21)00398-x ◽

2021 ◽

Vol 132 ◽

pp. S201

Author(s):

Guillermo Seratti ◽

Tiffany Pang ◽

Vikram Pansare ◽

Emanuela Izzo ◽

William Mackenzie ◽

...

Keyword(s):

Skeletal Dysplasia ◽

Clinical Utility ◽

Gene Panel ◽

Testing Program ◽

Panel Testing ◽

Gene Panel Testing

Download Full-text

Clinical implementation of gene panel testing for lysosomal storage diseases

Molecular Genetics & Genomic Medicine ◽

10.1002/mgg3.527 ◽

2018 ◽

Vol 7 (2) ◽

Cited By ~ 2

Author(s):

Alexander Gheldof ◽

Sara Seneca ◽

Katrien Stouffs ◽

Willy Lissens ◽

Anna Jansen ◽

...

Keyword(s):

Lysosomal Storage Diseases ◽

Gene Panel ◽

Lysosomal Storage ◽

Clinical Implementation ◽

Storage Diseases ◽

Panel Testing ◽

Gene Panel Testing

Download Full-text

MS3-1 IMPLEMENTATION OF GENE PANEL TESTING USING NEXT-GENERATION SEQUENCING

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.011 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii3-ii3

Author(s):

Kazuko Sakai

Keyword(s):

Cancer Treatment ◽

Gene Mutation ◽

Diagnostic Testing ◽

Gene Panel ◽

Panel Testing ◽

Formalin Fixed Paraffin ◽

Gene Panel Testing ◽

Companion Diagnostic ◽

Formalin Fixed Paraffin Embedded ◽

Formalin Fixed

Abstract The advance of next-generation sequencers (NGS) has dramatically improved the performance of genomic analysis of clinical samples in cancer precision medicine. The practical use of gene panel testing for clinical applications has begun in Japan. At present, “OncomineTM Dx Target Test” is listed as a companion diagnostic system using NGS, and “FoundationOne CDx Cancer Genomic Profile” and “OncoGuide™ NCC Oncopanel System” are listed as gene panel testing under insurance coverage. Formalin-fixed paraffin-embedded specimen have been routinely used for molecular diagnosis testing, therefore quality control such as formalin fixation time and tumor contents is important to ensure validity of diagnostic results. In this presentation, the issue to obtain evaluable results of gene panel testing using formalin-fixed paraffin-embedded specimen will be discussed. Due to evolution of detection technologies, we can detect gene mutation with high sensitivity. Detection of gene mutation in circulating tumor DNA is feasible approach for diagnostic testing in cancer treatment. Liquid biopsy has been approved as a companion diagnostic testing to detect EGFR mutations in NSCLC. Examples of the clinical utility of plasma testing in cancer treatment will be presented.

Download Full-text

167P Role of the multi-gene panel testing for detection of pathogenic variants in patients with hereditary bilateral breast cancer

Annals of Oncology ◽

10.1016/j.annonc.2021.08.448 ◽

2021 ◽

Vol 32 ◽

pp. S432-S433

Author(s):

C. Filorizzo ◽

D. Fanale ◽

L. Incorvaia ◽

N. Barraco ◽

M. Bono ◽

...

Keyword(s):

Breast Cancer ◽

Bilateral Breast Cancer ◽

Gene Panel ◽

Panel Testing ◽

Pathogenic Variants ◽

Gene Panel Testing

Download Full-text

Multi gene panel testing for hereditary breast cancer - is it ready to be used?

Medicine and Pharmacy Reports ◽

10.15386/mpr-1083 ◽

2019 ◽

Cited By ~ 1

Author(s):

Andreea Catana ◽

Adina Patricia Apostu ◽

Razvan-Geo Antemie

Keyword(s):

Breast Cancer ◽

Hereditary Breast Cancer ◽

Gene Panel ◽

Variants Of Uncertain Significance ◽

Panel Testing ◽

Brca Genes ◽

Prophylactic Measures ◽

Gene Panel Testing ◽

Uncertain Significance ◽

High Level

Breast cancer is one of the most common malignancies and the leading cause of death among women worldwide. About 20% of breast cancers are hereditary. Approximately 30% of the mutations have remained negative after testing BRCA1/2 even in families with a Mendelian inheritance pattern for breast cancer. Additional non-BRCA genes have been identified as predisposing for breast cancer. Multi gene panel testing tries to cover and explain the BRCA negative inherited breast cancer, improving efficiency, speed and costs of the breast cancer screening. We identified 23 studies reporting results from individuals who have undergone multi gene panel testing for hereditary breast cancer and noticed a prevalence of 1-12% of non-BRCA genes, but also a high level of variants of uncertain significance. A result with a high level of variants of uncertain significance is likely to be more costly than bring benefits, as well as increase the anxiety for patients. Regarding further development of multi gene panel testing, more research is required to establish both the optimal care of patients with cancer (specific treatments like PARP inhibitors) and the management of unaffected individuals (chemoprevention and/or prophylactic surgeries). Early detection in these patients as well as prophylactic measures will significantly increase the chance of survival. Therefore, multi gene panel testing is not yet ready to be used outside clear guidelines. In conclusion, studies on additional cohorts will be needed to better define the real prevalence, penetrance and the variants of these genes, as well as to describe clear evidence-based guidelines for these patients.

Download Full-text