f*********1
发帖数: 189 | 1 响应号召，参加[医学文献阅读活动]，
贴个icetea喜欢的，哈哈，4天前的Nature 关于 breast cancer的
The genomic and transcriptomic architecture of 2,000 breast tumours reveals
novel subgroups
Nature
(2012)
doi:10.1038/nature10983
Published online
18 April 2012
The elucidation of breast cancer subgroups and their molecular drivers
requires integrated views of the genome and transcriptome from
representative numbers of patients. We present an integrated analysis of
copy number and gene expression in a discovery and validation set of 997 and
995 primary breast tumours, respectively, with long-term clinical follow-up
. Inherited variants (copy number variants and single nucleotide
polymorphisms) and acquired somatic copy number aberrations (CNAs) were
associated with expression in ~40% of genes, with the landscape dominated by
cis- and trans-acting CNAs. By delineating expression outlier genes driven
in cis by CNAs, we identified putative cancer genes, including deletions in
PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles
revealed novel subgroups with distinct clinical outcomes, which reproduced
in the validation cohort. These include a high-risk, oestrogen-receptor-
positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup
devoid of CNAs. Trans-acting aberration hotspots were found to modulate
subgroup-specific gene networks, including a TCR deletion-mediated adaptive
immune response in the ‘CNA-devoid’ subgroup and a basal-specific
chromosome 5 deletion-associated mitotic network. Our results provide a
novel molecular stratification of the breast cancer population, derived from
the impact of somatic CNAs on the transcriptome. | f*********1
发帖数: 189 | 2 (CBS News) "Breast cancer" may be an inaccurate blanket term for ten
separate diseases, according to a new study in Nature.
Researchers looked at breast cancers in 2,000 women from the U.K. and Canada
and realized that the cancers, while under one unifying kind of disease,
have distinct subtypes. Because hospitals often cast a wide net of tests and
don't break down the kind of breast cancer further from their broad
categorizations, treatments might not be as specialized as they could be,
the researchers said.
"Based on our results we've reclassified breast cancer into 10 types -
making breast cancer an umbrella term for an even greater number of diseases
," study co-leader Carlos Caldas, senior group leader at Cancer Research UK'
s Cambridge Research Institute and the Department of Oncology at the
University of Cambridge, said in the press release. "Essentially we've moved
from knowing what a breast tumor looks like under a microscope to
pinpointing its molecular anatomy - and eventually we'll know which drugs it
will respond to."
Breast cancer is normally classified by "markers" on tumors and treatment
varies depending on this information. For example, those diseases with
estrogen receptors should respond to hormone therapies such as tamoxifen;
those with a so-called "Her2 recepto" can be treated with Herceptin, BBC
News reported.
Seventy percent of breast cancers respond to hormone therapies, but
reactions can vary. That's why, Caldas told BBC, being able to break down
specifically what kind of disease is affecting the patient could be crucial,
calling it a "completely new way of looking at breast cancer."
"This will change the way we look at breast cancer, it will have an enormous
impact in the years to come in diagnosing and treating breast cancer," Dr.
Harpal Kumar, chief executive for the non-profit Cancer Research UK, said to
BBC. The organization partially funded the study. "We think this is a
landmark study"
The information is supposed to impact how breast cancer is treated in future
generations.
"This research won't affect women diagnosed with breast cancer today,"
Caldas told Reuters. "But in the future, .. patients will receive treatment
targeted to the genetic fingerprint of their tumor."
Breast cancer will affect 229,060 Americans and cause about 39,920 deaths in
2012, according to the National Cancer Institute. | f*********1
发帖数: 189 | 3 Breast cancer breakthrough announced - thanks to Cambridge-led study
Carlos Caldas
Carlos Caldas
A major breakthrough in the treatment of breast cancer has been announced
today - thanks to a groundbreaking study led by a team of scientists in
Cambridge.
Researchers have reclassified breast cancers into 10 completely new
categories based on their genetic "fingerprints".
Several entirely new breast cancer genes that drive the disease have also
been uncovered.
The wealth of new data is expected to lead to better ways of predicting
patient survival, as well as novel treatments tailored to people’s genetic
make-up.
The research, published in the journal Nature, is the largest ever global
study of breast cancer tissue.
It marks the culmination of decades of work by British and Canadian
scientists led by a Cancer Research UK team based in Cambridge.
Genetic material from 2,000 tumour samples taken from women diagnosed with
breast cancer between five and 10 years ago was analysed in the study.
The scientists sorted the samples into 10 subtypes based on common genetic
features linked to survival. The new classification has major implications
for drug treatment, paving the way to more personalised therapies.
All the breast cancer genes identified by the scientists are potential
targets for the development of new drugs.
Links between these genes and known cell signalling pathways - the networks
that control cancer growth - were also revealed. This will make it easier to
pinpoint how the faulty genes cause cancer.
Professor Carlos Caldas, senior group leader at Cancer Research UK’s
Cambridge Research Institute, said: "Our results will pave the way for
doctors in the future to diagnose the type of breast cancer a woman has, the
types of drugs that will work, and those that won’t, in a much more
precise way than is currently possible.
"This research won’t affect women diagnosed with breast cancer today. But
in the future, breast cancer patients will receive treatment targeted to the
genetic fingerprint of their tumour.
"We’ve drilled down into the fundamental detail of the biological causes of
breast cancer in a comprehensive genetic study. Based on our results we’ve
reclassified breast cancer into 10 types - making breast cancer an umbrella
term for an even greater number of diseases.
"Essentially we’ve moved from knowing what a breast tumour looks like under
a microscope to pinpointing its molecular anatomy - and eventually we’ll
know which drugs it will respond to."
The next stage is to discover how tumours in each subgroup behave - for
instance, whether they grow or spread slowly or quickly, he said.
More research was also needed to come up with the most effective treatment
strategies for each of the 10 subgroups.
Co-author Professor Samuel Aparicio, from the BC Cancer Agency in Vancouver,
Canada, said: "Breast cancer is a global problem and it’s exciting to see
a new framework for the understanding of breast cancer emerge from our
partnership with colleagues in the UK.
"The new molecular map of breast cancer points us to new drug targets for
treating breast cancer and also defines the groups of patients who would
benefit most."
"The size of this study is unprecedented and provides insights into the
disease such as the role of immune response, which will stimulate other
avenues of research."
Dr Harpal Kumar, chief executive of Cancer Research UK, said: "This landmark
study will completely change the way we look at breast cancer. It’s the
result of decades of research by our scientists to identify the causes and
drivers of the disease, which included a pivotal role in decoding the well-
known BRCA genes.
"We’re entirely funded by the generosity of the public and this incredible
support has put us at the heart of progress that’s underpinned the dramatic
increase in the number of women surviving from breast cancer in the UK.
This new study will enable us to make a further step-change for patients
with breast cancer."
Personalised cancer treatments suited to people with specific genetic make-
ups have already been developed.
One of the best known is Herceptin, which is used to treat women with breast
cancer who have a faulty Her2 gene. | A*******s
发帖数: 9638 | | I****a
发帖数: 407 | 5 Nice post.
No disrespect to breast cancer patients but I think there is too much
emphasis on breast cancer in comparison to other type cancer especially ones
that are smoking related.
I do believe genetics plays a huge role in carcinogenesis but it is not
everything. Below is a slide from my previous talk for local Chinese
community.
【在 A*******s 的大作中提到】
: Thanks for sharing。
: Do you believe all disease is genetic？
: http://www.genomenewsnetwork.org/articles/10_00/Eisenberg_intro
| A*******s
发帖数: 9638 | 6 赞社区服务。
So icetea says Genetics is not everything, lol
ones
【在 I****a 的大作中提到】
: Nice post.
: No disrespect to breast cancer patients but I think there is too much
: emphasis on breast cancer in comparison to other type cancer especially ones
: that are smoking related.
: I do believe genetics plays a huge role in carcinogenesis but it is not
: everything. Below is a slide from my previous talk for local Chinese
: community.
| R*******t
发帖数: 367 | 7 大部分的新乳癌患者并无家庭病史。
【在 A*******s 的大作中提到】
: 赞社区服务。
: So icetea says Genetics is not everything, lol
:
: ones
| A*******s
发帖数: 9638 | 8 But they still could have a genetic disease.
【在 R*******t 的大作中提到】
: 大部分的新乳癌患者并无家庭病史。
| R*******t
发帖数: 367 | 9 Very true! Too bad they won't be qualified to have genetic testing until
several first degree relatives had breast cancer.
【在 A*******s 的大作中提到】
: But they still could have a genetic disease.
| A*******s
发帖数: 9638 | 10 Do you think the screening guideline should be revised? There was a lot of
controversy when the screen age was postponed.
【在 R*******t 的大作中提到】
: Very true! Too bad they won't be qualified to have genetic testing until
: several first degree relatives had breast cancer.
| R*******t
发帖数: 367 | 11 I am a strong advocate for annual screening from the age 40, or earlier if
there is strong family history of family cancer. Screening MRI should also
be considered when calculated Gail score of lifetime breast cancer risk more
than 25%.
A Sweden study with 30 years trial has proven screening mammogram does save
lives, and they only used one-view screening mammogram rather than The two-
views that we use here as standard protocol.
Now there are lots of debates if we should start from 50 or do it every
other year. I am against it. The onset of breast cancer seems to be younger
over the years, and the youngest patient I had was a 17 yo with invasive
ductal carcinoma and axillary nodal metastasis. And quite often, I see
cancer that has developed dramatically during a mere one year interval,
meaning the last year's mammogram was totally negative, and there is full-
blown cancer this year. Imagine how tragic it would be given two years for
aggressive cancers to grow in two years!
I do have some noncompliant patients who skip years when comes to their
yearly screen. Maybe once a month I see a cancer patient who skipped years,
and regretted so much about it. If you think about there are so many breast
imagers over the nation, how many patients we see all together that could
have been diagnosed earlier had they come to the screening mammogram every
single year? It matters so much to the health care fund in terms of
mortality and morbidity.
And I am not saying that because we make more money by screening every year.
Screening mammograms contribute very small portion of the revenue, about $
250 each, as compared to a stereotactic biopsy which is $7,000 each. If we
screen patients every other year, there would be more procedures, and fewer
subtle cancers we miss, which means less liability for us. But it hurts the
patients' best interests, it really does.
I would tell every female friends I know, that come to mammogram every year,
and treat our body the way it deserves to be treated, because you might be
the one who is lucky to find the cancer early enough to be cured.
【在 A*******s 的大作中提到】
: Do you think the screening guideline should be revised? There was a lot of
: controversy when the screen age was postponed.
| A*******s
发帖数: 9638 | 12 I hear you.
Have you read this article before?
Gøtzsche PC, Nielsen M (2011). "Screening for breast cancer with
mammography". Cochrane Database Syst Rev (1): CD001877. doi:10.1002/14651858
.CD001877.pub4. PMID 21249649.
more
save
younger
【在 R*******t 的大作中提到】
: I am a strong advocate for annual screening from the age 40, or earlier if
: there is strong family history of family cancer. Screening MRI should also
: be considered when calculated Gail score of lifetime breast cancer risk more
: than 25%.
: A Sweden study with 30 years trial has proven screening mammogram does save
: lives, and they only used one-view screening mammogram rather than The two-
: views that we use here as standard protocol.
: Now there are lots of debates if we should start from 50 or do it every
: other year. I am against it. The onset of breast cancer seems to be younger
: over the years, and the youngest patient I had was a 17 yo with invasive
| R*******t
发帖数: 367 | 13 Yes I have. The article had the conclusion over a 13-year followup, which is
not convincing. I will dig out Dr. Sickles's response to it when I get a
chance. A fun read.
14651858
【在 A*******s 的大作中提到】
: I hear you.
: Have you read this article before?
: Gøtzsche PC, Nielsen M (2011). "Screening for breast cancer with
: mammography". Cochrane Database Syst Rev (1): CD001877. doi:10.1002/14651858
: .CD001877.pub4. PMID 21249649.
:
: more
: save
: younger
|
|
