Cost-effectiveness of Genetic Testing of Endocrine Tumor Patients Using a Comprehensive Hereditary Cancer Gene Panel

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2024 May 3

PMID 38701358

Authors

Attila Patocs

Petra Nagy

Janos Papp

Aniko Bozsik

Balint Antal

Vince Kornel Grolmusz

Timea Pocza

Henriett Butz

Affiliations

Soon will be listed here.

Abstract

Introduction: Heterogenous clinical manifestations, overlapping phenotypes, and complex genetic backgrounds are common in patients with endocrine tumors. There are no comprehensive recommendations for genetic testing and counseling of these patients compared to other hereditary cancer syndromes. The application of multigene panel testing is common in clinical genetic laboratories, but their performance for patients with endocrine tumors has not been assessed.

Methods: As a national reference center, we prospectively tested the diagnostic utility and cost-efficiency of a multigene panel covering 113 genes representing genetic susceptibility for solid tumors; 1279 patients (including 96 cases with endocrine tumors) were evaluated between October 2021 and December 2022 who were suspected to have hereditary tumor syndromes.

Results: The analytical performance of the hereditary cancer panel was suitable for diagnostic testing. Clinical diagnosis was confirmed in 24% (23/96); incidental findings in genes not associated with the patient's phenotype were identified in 5% (5/96). A further 7% of pathogenic/likely pathogenic variants were detected in genes with potential genetic susceptibility roles but currently no clear clinical consequence. Cost-benefit analysis showed that the application of a more comprehensive gene panel in a diagnostic laboratory yielded a shorter turnaround time and provided additional genetic results with the same cost and workload.

Discussion: Using comprehensive multigene panel results in faster turnaround time and cost-efficiently identifies genetic alterations in hereditary endocrine tumor syndromes. Incidentally identified variants in patients with poor prognoses may serve as a potential therapeutic target in tumors where therapeutic possibilities are limited.

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References

Bychkovsky B, Agaoglu N, Horton C, Zhou J, Yussuf A, Hemyari P . Differences in Cancer Phenotypes Among Frequent CHEK2 Variants and Implications for Clinical Care-Checking CHEK2. JAMA Oncol. 2022; 8(11):1598-1606. PMC: 9501803. DOI: 10.1001/jamaoncol.2022.4071. View

Butz H, Nyiro G, Kurucz P, Liko I, Patocs A . Molecular genetic diagnostics of hypogonadotropic hypogonadism: from panel design towards result interpretation in clinical practice. Hum Genet. 2020; 140(1):113-134. PMC: 7864839. DOI: 10.1007/s00439-020-02148-0. View

Yohe S, Hauge A, Bunjer K, Kemmer T, Bower M, Schomaker M . Clinical validation of targeted next-generation sequencing for inherited disorders. Arch Pathol Lab Med. 2015; 139(2):204-10. DOI: 10.5858/arpa.2013-0625-OA. View

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17(5):405-24. PMC: 4544753. DOI: 10.1038/gim.2015.30. View

Rehm H, Bale S, Bayrak-Toydemir P, Berg J, Brown K, Deignan J . ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 2013; 15(9):733-47. PMC: 4098820. DOI: 10.1038/gim.2013.92. View

Tsaousis G, Papadopoulou E, Apessos A, Agiannitopoulos K, Pepe G, Kampouri S . Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. BMC Cancer. 2019; 19(1):535. PMC: 6547505. DOI: 10.1186/s12885-019-5756-4. View

Ullah A, Khan J, Waheed A, Sharma N, Pryor E, Stumpe T . Parathyroid Carcinoma: Incidence, Survival Analysis, and Management: A Study from the SEER Database and Insights into Future Therapeutic Perspectives. Cancers (Basel). 2022; 14(6). PMC: 8946517. DOI: 10.3390/cancers14061426. View

Wells Jr S, Asa S, Dralle H, Elisei R, Evans D, Gagel R . Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015; 25(6):567-610. PMC: 4490627. DOI: 10.1089/thy.2014.0335. View

Bahcall O . Genetic testing. ACMG guides on the interpretation of sequence variants. Nat Rev Genet. 2015; 16(5):256-7. DOI: 10.1038/nrg3940. View

10.

Brock P, Geurts J, van Galen P, Blouch E, Welch J, Kunz A . HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Challenges and opportunities in genetic counseling for hereditary endocrine neoplasia syndromes. Endocr Relat Cancer. 2020; 27(8):T65-T75. DOI: 10.1530/ERC-19-0454. View

11.

Houge G, Laner A, Cirak S, de Leeuw N, Scheffer H, den Dunnen J . Stepwise ABC system for classification of any type of genetic variant. Eur J Hum Genet. 2021; 30(2):150-159. PMC: 8821602. DOI: 10.1038/s41431-021-00903-z. View

12.

Petr E, Else T . Adrenocortical carcinoma (ACC): When and why should we consider germline testing?. Presse Med. 2018; 47(7-8 Pt 2):e119-e125. DOI: 10.1016/j.lpm.2018.07.004. View

13.

Jouinot A, Armignacco R, Assie G . Genomics of benign adrenocortical tumors. J Steroid Biochem Mol Biol. 2019; 193:105414. DOI: 10.1016/j.jsbmb.2019.105414. View

14.

OShea T, Druce M . When should genetic testing be performed in patients with neuroendocrine tumours?. Rev Endocr Metab Disord. 2017; 18(4):499-515. PMC: 5849652. DOI: 10.1007/s11154-017-9430-3. View

15.

Mattiuzzi C, Lippi G . Current Cancer Epidemiology. J Epidemiol Glob Health. 2019; 9(4):217-222. PMC: 7310786. DOI: 10.2991/jegh.k.191008.001. View

16.

Libe R . Adrenocortical carcinoma (ACC): diagnosis, prognosis, and treatment. Front Cell Dev Biol. 2015; 3:45. PMC: 4490795. DOI: 10.3389/fcell.2015.00045. View

17.

Lu E, Hatchell K, Nielsen S, Esplin E, Ouyang K, Nykamp K . Fumarate hydratase variant prevalence and manifestations among individuals receiving germline testing. Cancer. 2021; 128(4):675-684. PMC: 9170268. DOI: 10.1002/cncr.33997. View

18.

Sivakumaran T, Husami A, Kissell D, Zhang W, Keddache M, Black A . Performance evaluation of the next-generation sequencing approach for molecular diagnosis of hereditary hearing loss. Otolaryngol Head Neck Surg. 2013; 148(6):1007-16. DOI: 10.1177/0194599813482294. View

19.

Lincoln S, Hambuch T, Zook J, Bristow S, Hatchell K, Truty R . One in seven pathogenic variants can be challenging to detect by NGS: an analysis of 450,000 patients with implications for clinical sensitivity and genetic test implementation. Genet Med. 2021; 23(9):1673-1680. PMC: 8460443. DOI: 10.1038/s41436-021-01187-w. View

20.

Rehder C, Bean L, Bick D, Chao E, Chung W, Das S . Next-generation sequencing for constitutional variants in the clinical laboratory, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021; 23(8):1399-1415. DOI: 10.1038/s41436-021-01139-4. View