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IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2025-03-01 DOI:10.1002/mgg3.70086

Mathis Lepage, Nancy Uhrhammer, Ioana Molnar, Maud Privat, Flora Ponelle-Chachuat, Mathilde Gay-Bellile, Yannick Bidet, Mathias Cavaillé

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引用次数: 0

摘要

导言：多发性原发性恶性肿瘤（MPMs）是指同一患者体内有两个或两个以上的原发性恶性肿瘤。多发性恶性肿瘤的发病率很高：18.4%的癌症患者患有第二种或更多种原发性癌症。为了评估基因检测对多发性癌症患者的价值，需要进行研究以准确确定这些患者的致病变异的流行率：方法：2010 年至 2022 年期间，我们的肿瘤遗传学会诊中心接诊了所有家庭。我们比较了≥2种原发性癌症患者（n = 348）和单一原发性癌症患者（n = 1422）的临床特征和多达47个癌症易感基因的致病性或可能致病性变异的检出率：结果：在348名MPM指数患者中，27.3%的患者被诊断出致病或可能致病的变异基因，涉及21个基因：BRCA1 (n = 27)、BRCA2 (n = 19)、MSH2 (n = 9)、ATM (n = 8)、MLH1 (n = 5)、MSH6 (n = 6)、TP53 (n = 4)、CHEK2 (n = 4)、PALB2 (n = 3)、APC (n = 2)、MEN1 (n = 1)、RAD51C (n = 1)、NBN (n = 1)、EPCAM (n = 1)、PMS2 (n = 1)、RB1 (n = 1)、PTEN (n = 1)、CYLD1 (n = 1)、NF1 (n = 1)、RAD51D (n = 1) 和 CDKN2A (n = 1)。与单发癌症病例相比，MPM 指数病例更有可能携带有害突变（27.3% 对 11.39%，P 结论：与单发癌症病例相比，MPM 指数病例更有可能携带有害突变（27.3% 对 11.39%，P 结论）：与单发原发性癌症患者相比，转诊进行肿瘤基因检测的 MPM 患者更有可能携带癌症易感基因中的致病变异（p

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Prevalence of Constitutional Pathogenic Variant in a Cohort of 348 Patients With Multiple Primary Cancer Addressed in Oncogenetic Consultation.

Introduction: Multiple primary malignancies (MPMs) refer to two or more primary malignant tumors in the same patient. MPMs are frequent: 18.4% of incident cancers represent a second or a higher primary cancer. In order to assess the value of genetic testing for patients with multiple cancers, studies are needed to accurately determine the prevalence of pathogenic variants for these patients.

Methods: All families were seen in our oncogenetics consultation from 2010 to 2022. We compared clinical features and detection rates of pathogenic or likely pathogenic variants in a panel of up to 47 cancer predisposition genes in patients with ≥ 2 primary cancers (n = 348) versus a single primary cancer (n = 1422).

Results: A pathogenic or likely pathogenic variant was diagnosed in 27.3% of patients with 348 index patients with MPM, concerning 21 genes: BRCA1 (n = 27), BRCA2 (n = 19), MSH2 (n = 9), ATM (n = 8), MLH1 (n = 5), MSH6 (n = 6), TP53 (n = 4), CHEK2 (n = 4), PALB2 (n = 3), APC (n = 2), MEN1 (n = 1), RAD51C (n = 1), NBN (n = 1), EPCAM (n = 1), PMS2 (n = 1), RB1 (n = 1), PTEN (n = 1), CYLD1 (n = 1), NF1 (n = 1), RAD51D (n = 1), and CDKN2A (n = 1). MPM index cases were more likely to carry a deleterious mutation than cases with a single cancer (27.3% vs. 11.39%, p < 0.001). Pathogenic variants were found more frequently in patients with a suggestive family history (34.2% vs. 20.1%, p < 0.05), with a younger age of cancer diagnosis related to the suspected syndrome (32.7% vs. 22%, p = 0.049). For the 208 index patients with ≥ 2 cancers pertaining to the same predisposition syndrome (HBOC, HNPCC…), the detection rate increased significantly to 36% (vs. 14.3% for MPM patients with unrelated cancers (n = 140), p < 0.001). Conversely, the detection rate for patients with unrelated cancers was not statistically different from the single-cancer population (14.3%-11.39%, p = 0.318).

Conclusion: Patients referred for oncogenetic testing with MPM are more likely to carry pathogenic variants in cancer predisposition genes than patients with a single primary cancer (p < 0.05), especially if the cancers are related to the same predisposition syndrome. If the cancers are unrelated, no statistical difference in comparison to the single-cancer population was observed. For these latter patients, we recommend using the specific criteria of each tumor to propose appropriate genetic testing.

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.