Giersch Rachael M, Sevigny Jordana K, Weinandt Sydney A, Mayo Carissa, Garrett Fiona E S, Tindbaek Karyn, Yonemitsu Marisa A, Hart Samuel F M, Metzger Michael J
Pacific Northwest Research Institute, Seattle, Washington, United States of America.
Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.
PLoS Pathog. 2025 Sep 29;21(9):e1013537. doi: 10.1371/journal.ppat.1013537. eCollection 2025 Sep.
Bivalve transmissible neoplasias (BTNs) are leukemia-like cancers found in at least 10 bivalve species, in which the cancer cells themselves transfer from one individual to another, spreading as an unusual form of infectious disease. Before the infectious etiology was known, there were reports of lethality and outbreaks of cancer in the soft-shell clam (Mya arenaria) on the east coast of North America. Using sensitive and specific qPCR assays, we followed the outcomes of BTN in naturally-infected soft-shell clams from Maine, USA. We observed variable outcomes, with about half of clams (9/21) progressing to high levels of cancer and death, about half exhibiting long-term non-progression (11/21), and a single animal showing regression of cancer. We also observe a significant decrease in survival in animals that progress to >10% cancer in their hemolymph, while we see no effect on survival in clams with BTN that are long-term non-progressors. As most bivalves do not physically contact each other, and BTN cells can survive in seawater, it has been proposed that BTN is spread through release of cancer cells into the water. We used qPCR to detect BTN-specific sequences in environmental DNA (eDNA) in the tanks of animals throughout this experiment. We show that BTN-specific eDNA (likely from released cancer cells) can be detected in tank water of most clams with >24% cancer in their hemolymph, but not below this level. This detection of BTN eDNA is variable and occurs in bursts, but in clams with >24% cancer, the detection of BTN eDNA correlates with progression of the cancer in the hemolymph. This study demonstrates the lethality of BTN, but the observation that about half of clams with BTN do not progress to death provides evidence suggesting that there may be a block to the progression of BTN in a large portion of clams in a population with this enzootic disease. This study also further supports the hypothesis that BTN cells transmit through seawater and provides insights into the mechanisms of the transmission dynamics.
双壳贝类传染性肿瘤（BTNs）是在至少10种双壳贝类中发现的白血病样癌症，其中癌细胞本身从一个个体转移到另一个个体，以一种不寻常的传染病形式传播。在其感染性病因被发现之前，就有关于北美东海岸软壳蛤（砂海螂）致死率和癌症爆发的报道。我们使用灵敏且特异的定量聚合酶链反应（qPCR）检测方法，追踪了美国缅因州自然感染BTN的软壳蛤的病情发展。我们观察到了不同的结果，约一半的蛤（9/21）发展为癌症晚期并死亡，约一半表现为长期病情无进展（11/21），还有一只动物的癌症出现了消退。我们还观察到，血淋巴中癌症比例超过10%的动物存活率显著下降，而对于长期病情无进展的患BTN蛤，我们未发现其存活率受到影响。由于大多数双壳贝类不会相互直接接触，且BTN细胞能在海水中存活，因此有人提出BTN是通过癌细胞释放到水中来传播的。在整个实验过程中，我们使用qPCR检测动物养殖水箱环境DNA（eDNA）中的BTN特异性序列。我们发现，在血淋巴中癌症比例超过24%的大多数蛤的养殖水箱水中，可以检测到BTN特异性eDNA（可能来自释放的癌细胞），但低于此水平则检测不到。BTN eDNA的这种检测结果是可变的，且呈间歇性出现，但在血淋巴中癌症比例超过24%的蛤中，BTN eDNA的检测与血淋巴中癌症的进展相关。这项研究证明了BTN的致死性，但约一半患BTN的蛤未发展至死亡这一观察结果表明，在患有这种地方病的蛤群体中，很大一部分蛤的BTN病情发展可能存在阻碍。这项研究还进一步支持了BTN细胞通过海水传播的假说，并为传播动力学机制提供了见解。
