{"id":423,"title":"Telomere length of both parents contributes to heritable POT1 cancer-predisposition syndrome","title_zh":"父母双方端粒长度共同影响可遗传的POT1癌症易感综合征","url":"https://pubmed.ncbi.nlm.nih.gov/42875414","doi":"10.1038/s41467-026-77414-2","pmid":"42875414","journal":"Nat Commun","kind":"paper","lang":"en","published_at":"2026-09-14T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Martin A","Lu R","Blake A","Nichols KE","Sanchez SE","Artandi SE","Savage SA","Sharma R","Hockemeyer D"],"primary_topic":"repro-aging","topics":[{"slug":"repro-aging","score":4.0,"hits":["telomere"]},{"slug":"ivg-stem","score":1.0,"hits":["germline"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":72.0,"final_score":80.0,"score_dims":{"novelty":82,"rigor":75,"impact":65,"relevance":48,"translation":45},"recommend_reason":"该研究用单倍型分辨的纳米孔测序揭示POT1突变家族中端粒的双亲传递规律，并提出遗传早现机制，方法学与概念均有新意。但其核心是肿瘤易感与端粒生物学，与辅助生殖及胚胎研究的直接关联有限，对ART实验室的即时可用性不高。","keywords":["POT1","端粒长度","遗传早现","纳米孔测序","癌症易感综合征"],"selected":1,"story_id":440,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"nat-commun","journal_tier":"cns-sub","journal_if":14.7,"is_mock":false,"summary_zh":"本研究聚焦携带POT1胚系突变的家族，采用可提供单倍型特异性端粒长度分辨率的纳米孔测序方法，追踪端粒在亲子间的传递。结果显示，子代优先从携带突变的亲本继承最长端粒，而从非携带亲本继承的端粒相对较短；对携带者与非携带者同胞的比较进一步表明，携带者中来自父母双方的端粒均被延长，且最短端粒优先延长。作者据此提出遗传早现的潜在机制：POT1突变使携带者生殖系中能够执行端粒性肿瘤抑制的短端粒逐步耗竭，父母双方来源的端粒共同塑造端粒相关的肿瘤抑制屏障。","summary":"Germline and somatic mutations in POT1 promote oncogenesis by enabling aberrant telomere elongation. For inherited POT1 mutations, it remains unclear whether elongated telomeres are transmitted to the next generation and whether the inherited long telomeres elevate cancer risk. Using a nanopore sequencing approach that provides haplotype-specific telomere length resolution, we examined telomere inheritance in families carrying POT1 mutations. We found that offspring preferentially inherit their longest telomeres from the carrier parent, consistent with extensive germline telomere elongation, whereas comparatively short telomeres predominantly derive from the non-carrier parent. Analysis of carrier and non-carrier siblings demonstrated that telomeres from both parents are elongated in POT1 carriers, with preferential elongation of the shortest telomeres. These findings support a potential mechanism of genetic anticipation in which POT1 mutations progressively deplete short telomeres capable of enforcing telomere-based tumor suppression from the carrier germline. Therefore, telomeres inherited from both parents jointly shape telomere-based tumor suppressive barriers.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}