【bio-news】霍奇金淋巴瘤研究发现：“垃圾DNA”促进了肿瘤生长

'Junk DNA' Drives Cancer Growth, Hodgkin's Lymphoma Study Finds


ScienceDaily (May 3, 2010) — Researchers from the University of Leeds, UK, the Charité University Medical School and the Max Delbrück Centre for Molecular Medicine (MDC) in Berlin, Germany, have discovered a new driving force behind cancer growth.

Their studies have identified how 'junk' DNA promotes the growth of cancer cells in patients with Hodgkin's lymphoma. Professor Constanze Bonifer (University of Leeds) and Dr Stephan Mathas (Charité, MDC) who co-led the study suspect that these pieces of 'junk' DNA, called 'long terminal repeats', can play a role in other forms of cancer as well. The work is published in Nature Medicine.
The researchers uncovered the process by which this 'junk DNA' is made active, promoting cancer growth.
"We have shown this is the case in Hodgkin's lymphoma, but the exact same mechanism could be involved in the development of other forms of blood cancer," said Prof. Bonifer. "This would have implications for diagnosis, prognosis, and therapy of these diseases."
'Long terminal repeats' (LTRs) are a form of 'junk DNA' -- genetic material that has accumulated in the human genome over millions of years. Although LTRs originate from viruses and are potentially harmful, they are usually made inactive when embryos are developing in the womb.
If this process of inactivation doesn't work, then the LTRs could activate cancer genes, a possibility that was suggested in previous animal studies. This latest research has now demonstrated for the first time that these 'rogue' active LTRs can drive the growth of cancer in humans.
The work focused on cancerous cells of Hodgkin's lymphoma (the Hodgkin-/Reed Sternberg cells) that originate from white blood cells (antibody-producing B cells). Unusually, this type of lymphoma cell does not contain a so-called 'growth factor receptor' that normally controls the growth of other B-cells.
They found that the lymphoma cells' growth was dependent on a receptor that normally regulates the growth of other immune cells, but it is not usually found in B-cells. However in this case, the Hodgkin-/Reed Sternberg cells 'hijacked' this receptor for their own purposes by activating some of the 'junk DNA'. In fact the lymphoma cells activated hundreds, if not thousands, of LTRs all over the genome, not just one.
Hodgkin-/Reed Sternberg cells may not be the only cells that use this method to subvert normal controls of cell growth. The researchers found evidence of the same LTRs activating the same growth receptor in anaplastic large cell lymphoma, another blood cancer.
The consequences of such widespread LTR activation are currently still unclear, according to the study's authors. Such processes could potentially activate other genes involved in tumour development. It could also affect the stability of chromosomes of lymphoma cells, a factor that may explain why Hodgkin-/Reed Sternberg cells gain many chromosomal abnormalities over time and become more and more malignant.
Background
1. There are about 1,300 new cases of Hodgkin's lymphoma each year in the UK, including 150 in children.
2. LTR fragments were originally formed by infection with retroviruses, a type of virus that can integrate their own genetic material into a host gene. The human genome contains thousands of these LTR fragments.
3. The receptor that was observed to control cell growth in Hodgkin-/Reed Sternberg cells is known as CSF1R (the colony stimulating factor 1 receptor).

http://www.sciencedaily.com/releases/2010/05/100502173845.htm

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'Junk DNA' Drives Cancer Growth, Hodgkin's Lymphoma Study Finds
ScienceDaily (May 3, 2010) — Researchers from the University of Leeds, UK, the Charité University Medical School and the Max Delbrück Centre for Molecular Medicine (MDC) in Berlin, Germany, have discovered a new driving force behind cancer growth.

霍奇金淋巴瘤研究发现：“垃圾DNA”促进了肿瘤生长

译者：Docofsoul



《每日科学》2010年5月3日报道 —— 来自英国利兹大学、德国柏林查理特大学与德国柏林Max Delbrück分子医学中心（MDC）的研究人员发现了一种新的肿瘤生长驱动力。

Their studies have identified how 'junk' DNA promotes the growth of cancer cells in patients with Hodgkin's lymphoma. Professor Constanze Bonifer (University of Leeds) and Dr Stephan Mathas (Charité, MDC) who co-led the study suspect that these pieces of 'junk' DNA, called 'long terminal repeats', can play a role in other forms of cancer as well. The work is published in Nature Medicine.

他们的研究证实了“垃圾”DNA促进霍奇金淋巴瘤病人的肿瘤细胞生长的方式与途径。Constanze Bonifer教授（利兹大学）与Stephan Mathas博士（查理特大学与MDC）共同率队领导了这一研究，他们怀疑这些称之为“长末端重复”的“垃圾”DNA碎片在其它形式的肿瘤中也起了作用。该研究成果发表于《自然医学》（Nature Medicine）杂志上。

The researchers uncovered the process by which this 'junk DNA' is made active, promoting cancer growth.

研究者提示了该“垃圾DNA”被激活后促进肿瘤生长的过程。

"We have shown this is the case in Hodgkin's lymphoma, but the exact same mechanism could be involved in the development of other forms of blood cancer," said Prof. Bonifer. "This would have implications for diagnosis, prognosis, and therapy of these diseases."
'Long terminal repeats' (LTRs) are a form of 'junk DNA' -- genetic material that has accumulated in the human genome over millions of years. Although LTRs originate from viruses and are potentially harmful, they are usually made inactive when embryos are developing in the womb.

Bonifer教授说：“我们已经显示这是霍奇金淋巴瘤中所发生的情形。但在其它形式的血液肿瘤中也可能涉及完全相同的机制。 本发现对这些疾病的诊断、预后与治疗都有意义。” “长末端重复”（LTRs）是“垃圾DNA”的一种形式。“垃圾DNA”是指几百万年来累积于人类基因组里的遗传物质。虽然LTRs产生于病毒同时也是潜在有害的，但胚胎在子宫内发育时垃圾DNA并不活动。

If this process of inactivation doesn't work, then the LTRs could activate cancer genes, a possibility that was suggested in previous animal studies. This latest research has now demonstrated for the first time that these 'rogue' active LTRs can drive the growth of cancer in humans.

此前动物研究提示：如果这一失活过程不起作用的话，那么LTRs就会激发肿瘤基因。这项最新的研究则首次展示了这些形同“无赖”的活动LTRs能够驱动人类肿瘤生长。

The work focused on cancerous cells of Hodgkin's lymphoma (the Hodgkin-/Reed Sternberg cells) that originate from white blood cells (antibody-producing B cells). Unusually, this type of lymphoma cell does not contain a so-called 'growth factor receptor' that normally controls the growth of other B-cells.

该研究工作的焦点是产生于白血球（能产生抗体的B细胞）的霍奇金淋巴瘤（Hodgkin/Reed-Sternberg细胞）的癌细胞。不同寻常的是，该类型的淋巴瘤细胞不包含所谓的“生长因子受体”（此受体正常情形下控制其它B细胞生长）。

They found that the lymphoma cells' growth was dependent on a receptor that normally regulates the growth of other immune cells, but it is not usually found in B-cells. However in this case, the Hodgkin-/Reed Sternberg cells 'hijacked' this receptor for their own purposes by activating some of the 'junk DNA'. In fact the lymphoma cells activated hundreds, if not thousands, of LTRs all over the genome, not just one.

他们发现淋巴瘤细胞的生长依赖于一种正常情形下调节其它免疫细胞生长的受体，但B细胞中通常不会有该受体。不过在霍奇金淋巴瘤情形下，Hodgki-/Reed Sternberg cell细胞通过激活某些“垃圾DNA”“劫持”了该受体来为自己效劳。事实上，淋巴瘤细胞在整个基因组中激活了不只一个LTRs， 而是激活了即使没有数千、起码也有数百的LTRs。

Hodgkin-/Reed Sternberg cells may not be the only cells that use this method to subvert normal controls of cell growth. The researchers found evidence of the same LTRs activating the same growth receptor in anaplastic large cell lymphoma, another blood cancer.

Hodgkin/Reed Sternberg 细胞可能不是唯一用这种方法来颠覆正常细胞生长控制的细胞。研究者已发现相同的LTRs在间变性大细胞淋巴瘤（另外一种血癌）中激活了相同的生长感受器的证据。

The consequences of such widespread LTR activation are currently still unclear, according to the study's authors. Such processes could potentially activate other genes involved in tumour development. It could also affect the stability of chromosomes of lymphoma cells, a factor that may explain why Hodgkin-/Reed Sternberg cells gain many chromosomal abnormalities over time and become more and more malignant.

据该研究的作者介绍，这种广泛的LTR激活的后果目前尚不明朗。其过程可能有激活其它与肿瘤生长有关的基因的潜力。LTR激活也可能影响淋巴瘤细胞染色体的稳定性，从而可能解释了为何Hodgkin/Reed Sternberg细胞随着时间许多染色体出现异常从而变得越来越危险（即成为恶性肿瘤）。

Background
1. There are about 1,300 new cases of Hodgkin's lymphoma each year in the UK, including 150 in children.

背景资料：

1．英国每年出现1300个霍奇金淋巴瘤新病倒，其中包括150例儿童霍奇金淋巴瘤。

2. LTR fragments were originally formed by infection with retroviruses, a type of virus that can integrate their own genetic material into a host gene. The human genome contains thousands of these LTR fragments.

2．LTR碎片最初通过逆转录病毒的感染形成，这种病毒类型可将本身的遗传物质与宿主的基因结合为一体。人类基因组包含了数千这种LTR碎片。

3. The receptor that was observed to control cell growth in Hodgkin-/Reed Sternberg cells is known as CSF1R (the colony stimulating factor 1 receptor).

3．所观察到的Hodgkin/Reed Sternberg细胞中控制细胞生长的受体即是CSF1R (the colony stimulating factor 1 receptor，集落刺激因子-1受体).

（Docofsoul译于2010-5-4）

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霍奇金淋巴瘤研究发现：“垃圾DNA”促进了肿瘤生长

译者：Docofsoul



《每日科学》2010年5月3日报道 —— 来自英国利兹大学、德国柏林查理特大学与德国柏林Max Delbrück分子医学中心（MDC）的研究人员发现了一种新的肿瘤生长驱动力。

他们的研究证实了“垃圾”DNA促进霍奇金淋巴瘤病人的肿瘤细胞生长的方式与途径。Constanze Bonifer教授（利兹大学）与Stephan Mathas博士（查理特大学与MDC）共同率队领导了这一研究，他们怀疑这些称之为“长末端重复”的“垃圾”DNA碎片在其它形式的肿瘤中也起了作用。该研究成果发表于《自然医学》（Nature Medicine）杂志上。

研究者提示了该“垃圾DNA”被激活后促进肿瘤生长的过程。

Bonifer教授说：“我们已经显示这是霍奇金淋巴瘤中所发生的情形。但在其它形式的血液肿瘤中也可能涉及完全相同的机制。 本发现对这些疾病的诊断、预后与治疗都有意义。” “长末端重复”（LTRs）是“垃圾DNA”的一种形式。“垃圾DNA”是指几百万年来累积于人类基因组里的遗传物质。虽然LTRs产生于病毒同时也是潜在有害的，但胚胎在子宫内发育时垃圾DNA并不活动。

此前多项动物研究已经提示：如果这一失活过程不起作用的话，那么LTRs就会激发肿瘤基因。这项最新的研究则首次展示了这些形同“无赖”的活动LTRs能够驱动人类肿瘤生长。

该研究工作的焦点是产生于白血球（能产生抗体的B细胞）的霍奇金淋巴瘤（Hodgkin/Reed-Sternberg细胞）的癌细胞。不同寻常的是，该类型的淋巴瘤细胞并不包含所谓的“生长因子感受器”（此感受器正常情形下控制其它B细胞生长）。

他们发现淋巴瘤细胞的生长依赖于一种正常情形下调节其它免疫细胞生长的受体，但B细胞中通常不会有该受体。不过在霍奇金淋巴瘤情形下，Hodgki-/Reed Sternberg cell细胞通过激活某些“垃圾DNA”“劫持”了该受体来为自己效劳。事实上，淋巴瘤细胞在整个基因组中激活了不只一个LTRs， 而是激活了即使没有数千、起码也有数百的LTRs。

Hodgkin/Reed Sternberg 细胞可能不是唯一用这种方法来颠覆正常细胞生长控制的细胞。研究者已发现相同的LTRs在间变性大细胞淋巴瘤（另外一种血癌）中激活了相同的生长受体的证据。

据该研究的作者介绍，这种LTR广泛激活的后果目前尚不明朗。其过程可能有激活其它与肿瘤生长有关的基因的潜在能力。LTR激活也可能影响淋巴瘤细胞染色体的稳定性，从而可能解释了为何Hodgkin/Reed Sternberg细胞随着时间许多染色体出现异常从而变得越来越危险（即成为恶性肿瘤）。

背景资料介绍：

1．英国每年出现1300个霍奇金淋巴瘤新病倒，其中包括150例儿童霍奇金淋巴瘤。

2．LTR碎片最初通过逆转录病毒的感染形成，这种病毒类型可将本身的遗传物质与宿主的基因结合为一体。人类基因组包含了数千这种LTR碎片。

3．所观察到的Hodgkin/Reed Sternberg细胞中控制细胞生长的受体即是CSF1R (the colony stimulating factor 1 receptor，集落刺激因子-1受体).

（Docofsoul译于2010-5-4）